Sarcopenia,or muscle loss,has been one of the hot topics in the medical field in recent years.Due to limited attention and effective treatments for sarcopenia in the past,many patients,especially the elderly,suffered ...Sarcopenia,or muscle loss,has been one of the hot topics in the medical field in recent years.Due to limited attention and effective treatments for sarcopenia in the past,many patients,especially the elderly,suffered irreversible damage to their motor function caused by sarcopenia.However,recent scientific studies have found that the occurrence and development of sarcopenia are closely related to the function and quantity of muscle satellite cells.This article briefly discusses the relationship between muscle satellite cells and sarcopenia.展开更多
As the only source of stem cells, satellite cells play and extraordinary role in the remediation process of skeletal muscle after injury. This paper overviewed the biological characteristic of skeletal muscle satellit...As the only source of stem cells, satellite cells play and extraordinary role in the remediation process of skeletal muscle after injury. This paper overviewed the biological characteristic of skeletal muscle satellite cells and its role in repairing muscle injury, and put forward the prospects of its application in muscle trauma repair.展开更多
A synthetic isoflavone (ISO-S) or genistein was added in culture medium at different concentrations (0, 10, 20, 30, 40, and 80 p.mol L^-1) to investigate the effects of soybean isoflavones on antioxidative capacit...A synthetic isoflavone (ISO-S) or genistein was added in culture medium at different concentrations (0, 10, 20, 30, 40, and 80 p.mol L^-1) to investigate the effects of soybean isoflavones on antioxidative capacity of porcine skeletal muscle satellite cells. After 48 h incubation, the suspension was cryopreserved for the determination of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-Px) activities, and malondialdehyde (MDA) content. The mRNA levels of SOD, CAT, and GSH-Px gene in cells were detected with Taqman fluorescent probe method. The results showed that the content of MDA and the activities and the mRNA levels of SOD of porcine skeletal muscle satellite cells were influenced by supplemented soybean isoflavone (P〈0.05) when adding 10-80 μmol L^-1 ISO-S or genistein in the medium. The MDA contents, SOD and CAT activities and their mRNA expression levels of porcine skeletal muscle cells responded quadratically (P〈 0.05) as the level of ISO-S or genistein increased. Pre-incubation of porcine skeletal muscle satellite cells with ISO-S or genistein at 10-40 pmol L-1 elevated the activities and the mRNA expression levels of SOD and CAT in cells concurrently and decreased the cellular content of MDA (P〈 0.05). The results indicated that pre-incubation of ISO-S or genistein at 10- 40μmol L^-1 could improve the antioxidative capacity of porcine skeletal muscle satellite cells.展开更多
Pig is an important economic animal in China. Improving meat quality and meat productivity is a long time issue in animal genetic breeding. Micro RNAs(mi RNAs) are short non-coding RNAs that participate in various bio...Pig is an important economic animal in China. Improving meat quality and meat productivity is a long time issue in animal genetic breeding. Micro RNAs(mi RNAs) are short non-coding RNAs that participate in various biological processes, such as muscle development and embryogenesis. mi R-22 differentially expresses in embryonic and adult skeletal muscle. However, the underlying mechanism is unclear. In this study, we investigated mi R-22 function in proliferation and differentiation of porcine satellite cells(PSCs) in skeletal muscle. Our data show that mi R-22 expressed in both proliferation and differentiated PSCs and is significantly upregulated(P<0.05) during differentiation. After treated with the mi R-22 inhibitor, PSCs proliferation was significantly increased(P<0.05), as indicated by the up-regulation(P<0.01) of cyclin D1(CCND1), cyclin B1(CCNB1) and down-regulation(P<0.05) of P21. Conversely, over-expression of mi R-22 resulted in opposite results. Differentiation of PSCs was significantly suppressed(P<0.05), evidenced by two major myogenic markers: myogenin(Myo G) and myosin heavy chain(My HC), after transfecting the PSCs with mi R-22 inhibitor. Opposite results were demonstrated in the other way around by transfection with mi R-22 mimics. In conclusion, the data from this study indicated that mi R-22 inhibited the PSCs proliferation but promoted their differentiation.展开更多
Phosphatidylserine(PS)is distributed asymmetrically in the plasma membrane of eukaryotic cells.Phosphatidylserine flippase(P4-ATPase)transports PS from the outer leaflet of the lipid bilayer to the inner leaflet of th...Phosphatidylserine(PS)is distributed asymmetrically in the plasma membrane of eukaryotic cells.Phosphatidylserine flippase(P4-ATPase)transports PS from the outer leaflet of the lipid bilayer to the inner leaflet of the membrane to maintain PS asymmetry.TheβsubunitTMEM30 Ais indispensable for transport and proper function of P4-ATPase.Previous studies have shown that the ATP11 A and TMEM30 A complex is the molecular switch for myotube formation.However,the role of Tmem30 a in skeletal muscle regeneration remains elusive.In the current study,Tmem30 a was highly expressed in the tibialis anterior(TA)muscles of dystrophin-null(mdx)mice and BaCl2-induced muscle injury model mice.We generated a satellite cell(SC)-specific Tmem30 a conditional knockout(cKO)mouse model to investigate the role of Tmem30 a in skeletal muscle regeneration.The regenerative ability of cKO mice was evaluated by analyzing the number and diameter of regenerated SCs after the TA muscles were injured by BaCl2-injection.Compared to the control mice,the cKO mice showed decreased Pax7+and MYH3+SCs,indicating diminished SC proliferation,and decreased expression of muscular regulatory factors(MYOD and MYOG),suggesting impaired myoblast proliferation in skeletal muscle regeneration.Taken together,these results demonstrate the essential role of Tmem30 a in skeletal muscle regeneration.展开更多
To examine the effect of myogenin gene on the differentiation of bovine skeletal muscle satellite cell, we constructed small interfering RNA plasmid vector to obtain myogenin knockdown bovine skeletal muscle cells, th...To examine the effect of myogenin gene on the differentiation of bovine skeletal muscle satellite cell, we constructed small interfering RNA plasmid vector to obtain myogenin knockdown bovine skeletal muscle cells, then used cell transfection, real time RCR and Western Blot to detect the influence of myogenin to cell differentiation. Results showed that the knockdown of myogenin significantly decreased its expression and other muscle-specific genes. Compared to the control, it could differentiate into few myotubes when challenged by low serum in the medium. These findings provided an important theoretical basis for further explore of the genetic mechanism in adult skeletal muscle, the remedy of muscle injuries and the cultivation of high-yield transgenic cattle.展开更多
Background: Muscle growth depends on the fusion of proliferate satellite cells to existing myofibers. We reported previously that 0-14 day intermittent feeding led to persistent retardation in myofiber hypertrophy. H...Background: Muscle growth depends on the fusion of proliferate satellite cells to existing myofibers. We reported previously that 0-14 day intermittent feeding led to persistent retardation in myofiber hypertrophy. However, how satellite cells respond to such nutritional insult has not been adequately elucidated. Results: One-day-old broiler chicks were allocated to control (Con, ad libitum feeding), intermittent feeding (IF, feed provided on alternate days) and re-feeding (RF, 2 days ad libitum feeding after 12 days of intermittent feeding) groups. Chickens were killed on Day 15 and satellite cells were isolated. When cultured, satellite cells from the IF group demonstrated significant retardation in proliferation and differentiation potential, while RF partly restored the proliferation rate and differentiation potential of the satellite cells. Significant up-regulation of insulin like growth factor I receptor (IGF-IR) (P〈O.05) and thyroid hormone receptor o (TRo) (P〈O.05), and down-regulation of growth hormone receptor (GHR) (P〈O.01) and IGF-I (P〈O.01) mRNA expression was observed in freshly isolated IF satellite cells when compared with Con cells. In RF cells, the mRNA expression of IGF-I was higher (P〈O.05) and of TRa was lower (P〈O.01) than in IF cells, suggesting that RF restored the mRNA expression of TRa and IGF-I, but not of GHR and IGF-IR. The Bax/Bcl-2 ratio tended to increase in the IF group, which was reversed in the RF group (P〈O.05), indicating that RF reduced the pro-apoptotic influence of iF. Moreover, no significant effect of T3 was detected on cell survival in IF cells compared with Con (P〈O.O01) or RF (P〈O.05) cells. Conclusions: These data suggest that early-age feed restriction inhibits the proliferation and differentiation of satellite cells, induces changes in mRNA expression of the GH/IGF-I and thyroid hormone receptors in satellite cells, as well as blunted sensitivity of satellite cells to T3, and that RF partially reverses these effects. Thus, a moderate nutritional strategy for feed restriction should be chosen in early chick rearing systems.展开更多
Numerous physiological and pathological processes are controlled by free fatty acids, which act as signaling molecules in mammals. We hypothesized that oleic acid (Ole) might stimulate the formation of satellite-cell-...Numerous physiological and pathological processes are controlled by free fatty acids, which act as signaling molecules in mammals. We hypothesized that oleic acid (Ole) might stimulate the formation of satellite-cell-derived intramuscular adipose tissue. The role of Ole as a ligand of <em>G-protein-coupled receptor 43</em> (<em>GPR4</em>3) was previously identified. Thus, the objective of the current study was to determine the effect of Ole on <em>GPR43</em> and factors related to the adipogenic differentiation of bovine satellite cells (BSC). Treatments of 100 μM and 500 μM Ole tended to induce greater (P < 0.10) mRNA expression of <em>CCAAT/enhancer-binding protein β</em> (<em>C/EBPβ</em>) compared to all other doses. The mRNA abundance of peroxisome proliferator-activated receptor γ (<em>PPARγ</em>) was not altered (<em>P</em> > 0.10) by treatment. The addition of 100 μM and 500 μM of Ole upregulated (<em>P</em> < 0.05) <em>GPR43</em> mRNA expression. Protein level of GPR43 was increased (<em>P</em> < 0.05) by 100 μM of Ole treatments. Addition of Ole to BSC cultures induced transformation of myogenic cells into adipocyte-like cells that formed cytoplasmic lipid droplets. Increased expression of<em> C/EBPβ</em> in response to Ole might suppress myogenic differentiation. After the treatment of cells with Ole, increased expression of GPR43 could lead to phosphorylation of 5’ AMP-activated protein kinase α (AMPKα). Altogether, the results indicated that increased Ole might stimulate adipose tissue accumulation within the skeletal muscle of cattle by promoting adipogenic differentiation and activation of GPR43 in satellite cells.展开更多
This study investigated the protective effect of ATP on skeletal muscle satellite cells damaged by H2O2 in neonatal rats and the possible mechanism. The skeletal muscle satellite cells were randomly divided into four ...This study investigated the protective effect of ATP on skeletal muscle satellite cells damaged by H2O2 in neonatal rats and the possible mechanism. The skeletal muscle satellite cells were randomly divided into four groups: normal group, model group(cells treated with 0.1 mmol/L H2O2 for 50 s), protection group(cells treated with 16, 8, 4, 2, 1, 0.5, or 0.25 mmol/L ATP for 24 h, and then with 0.1 mmol/L H2O2 for 50 s), proliferation group(cells treated with 16, 8, 4, 2, 1, 0.5, or 0.25 mmol/L ATP for 24 h). MTT assay, FITC+PI+DAPI fluorescent staining, Giemsa staining and immunofluorescence were performed to examine cell viability and apoptosis, and apoptosis-related proteins. The results showed that the survival rate of skeletal muscle satellite cells was decreased and the apoptosis rate was increased after H2O2 treatment(P〈0.01). Different doses of ATP had different effects on skeletal muscle satellite cells damaged by H2O2: the survival rate of muscle satellite cells treated with ATP at 4, 2, or 1 mmol/L was increased. The protective effect was most profound on cells treated with 2 mmol/L ATP. Immunofluorescence showed that ATP could increase the number of Bcl-2-positive cells(P〈0.01) and decrease the number of the Bax-positive cells(P〈0.01). It was concluded that ATP could protect skeletal muscle satellite cells against H2O2 damage in neonatal rats, which may be attributed to the up-regulation of the expression of Bcl-2 and down-regulation of Bax, resulting in the suppression of apoptosis.展开更多
Objective To study the cell growth factor secretion and vascular regeneration in acute in-farcted myocardium after autologous skeletal muscle satellite cell implantation. Methods Autologous skeletal muscle satellite c...Objective To study the cell growth factor secretion and vascular regeneration in acute in-farcted myocardium after autologous skeletal muscle satellite cell implantation. Methods Autologous skeletal muscle satellite cells from adult mongrel canine were implanted into the acute myocardial infarct site via the ligated left anterior descending (LAD) artery. Specimens were harvested at 2, 4 , 8 weeks after implantation for the expression of insulin-like growth factor-1 (IGF-1), basic fibroblast growth factor ( bFGF) and the vascular density. Results The expression of IGF-1, bFGF and the vascular density in skeletal muscle satellite cell implant group were higher than that in the control group. Conclusion The skeletal muscle satellite cells, after being implanted into the acute myocardial infarction, not only showed myocardial regeneration, but also showed the ability to secrete the cell factors, hence representing a positive effect on the regeneration of the infarcted myocardium.展开更多
Objective To study the improvement of infarcted myocardial contractile force after autologous skeletal muscle satellite cell implantation via intracoronary arterial perfusion. Methods Skeletal muscle cells were harves...Objective To study the improvement of infarcted myocardial contractile force after autologous skeletal muscle satellite cell implantation via intracoronary arterial perfusion. Methods Skeletal muscle cells were harvested from gluteus max of adult mongrel dogs and the cells were cultured and expanded before being labeled with DAPI (4’, 6-diamidino-2-phenylindone). The labeled cells were then implanted into the acute myocardial infarct site via the ligated left anterior descending (LAD) coronary artery. Specimens were taken at 2nd, 4th, 8th week after myoblast implantation for histologic and contractile force evaluation, respectively. Results The satellite cells with fluorescence had been observed in the infarct site and also in papi- llary muscle with consistent oriented direction of host myocardium. A portion of the implanted cells had differen- tiated into muscle fibers. Two weeks after implantation, the myocardial contractile force showed no significant difference between the cell implant group and control group. At 4 and 8 week, the contractile force in the cell implant group was better than that in control group. Conclusion The skeletal muscle satellite cells, implanted into infarct myocardium by intracoronary arterial perfusion, could disseminate through the entire infarcted zone with myocardial regeneration and improve the contractile function of the infarcted myocardium.展开更多
The gut microbiota plays a pivotal role in systemic metabolic processes and in particular functions,such as developing and preserving the skeletal muscle system.However,the interplay between gut microbiota/metabolites...The gut microbiota plays a pivotal role in systemic metabolic processes and in particular functions,such as developing and preserving the skeletal muscle system.However,the interplay between gut microbiota/metabolites and the regulation of satellite cell(SC)homeostasis,particularly during aging,remains elusive.We propose that gut microbiota and its metabolites modulate SC physiology and homeostasis throughout skeletal muscle development,regeneration,and aging process.Our investigation reveals that microbial dysbiosis manipulated by either antibiotic treatment or fecal microbiota transplantation from aged to adult mice,leads to the activation of SCs or a significant reduction in the total number.Furthermore,employing multi-omics(e.g.,RNA-seq,16S r RNA gene sequencing,and metabolomics)and bioinformatic analysis,we demonstrate that the reduced butyrate levels,alongside the gut microbial dysbiosis,could be the primary factor contributing to the reduction in the number of SCs and subsequent impairments during skeletal muscle aging.Meanwhile,butyrate supplementation can mitigate the antibiotics-induced SC activation irrespective of gut microbiota,potentially by inhibiting the proliferation and differentiation of SCs/myoblasts.The butyrate effect is likely facilitated through the monocarboxylate transporter 1(Mct1),a lactate transporter enriched on membranes of SCs and myoblasts.As a result,butyrate could serve as an alternative strategy to enhance SC homeostasis and function during skeletal muscle aging.Our findings shed light on the potential application of microbial metabolites in maintaining SC homeostasis and preventing skeletal muscle aging.展开更多
Satellite glial cells are unique glial cells that surround the cell body of primary sensory neurons.An increasing body of evidence suggests that in the presence of inflammation and nerve damage,a significant number of...Satellite glial cells are unique glial cells that surround the cell body of primary sensory neurons.An increasing body of evidence suggests that in the presence of inflammation and nerve damage,a significant number of satellite glial cells become activated,thus triggering a series of functional changes.This suggests that satellite glial cells are closely related to the occurrence of chronic pain.In this review,we first summarize the morphological structure,molecular markers,and physiological functions of satellite glial cells.Then,we clarify the multiple key roles of satellite glial cells in chronic pain,including gap junction hemichannel Cx43,membrane channel Pannexin1,K channel subunit 4.1,ATP,purinergic P2 receptors,and a series of additional factors and their receptors,including tumor necrosis factor,glutamate,endothelin,and bradykinin.Finally,we propose that future research should focus on the specific sorting of satellite glial cells,and identify genomic differences between physiological and pathological conditions.This review provides an important perspective for clarifying mechanisms underlying the peripheral regulation of chronic pain and will facilitate the formulation of new treatment plans for chronic pain.展开更多
To uncover the role of satellite cells(SCs)in paravertebral muscle development and aging,we constructed a single-nucleus transcriptomic atlas of mouse paravertebral muscle across seven timepoints spanning the embryo(d...To uncover the role of satellite cells(SCs)in paravertebral muscle development and aging,we constructed a single-nucleus transcriptomic atlas of mouse paravertebral muscle across seven timepoints spanning the embryo(day 16.5)to old(month 24)stages.Eight cell types,including SCs,fast muscle cells,and slow muscle cells,were identified.An energy metabolism-related gene set,TCA CYCLE IN SENESCENCE,was enriched in SCs.Forty-two skeletal muscle disease-related genes were highly expressed in SCs and exhibited similar expression patterns.Among them,Pdha1 was the core gene in the TCA CYCLE IN SENESCENCE;Pgam2,Sod1,and Suclg1 are transcription factors closely associated with skeletal muscle energy metabolism.Transcription factor enrichment analysis of the 42 genes revealed that Myod1 and Mef2a were also highly expressed in SCs,which regulated Pdha1 expression and were associated with skeletal muscle development.These findings hint that energy metabolism may be pivotal in SCs development and aging.Three ligand-receptor pairs of extracellular matrix(ECM)-receptor interactions,Lamc1-Dag1,Lama2-Dag1,and Hspg2-Dag1,may play a vital role in SCs interactions with slow/fast muscle cells and SCs self-renewal.Finally,we built the first database of a skeletal muscle single-cell transcriptome,the Musculoskeletal Cell Atlas(http://www.mskca.tech),which lists 630,040 skeletal muscle cells and provides interactive visualization,a useful resource for revealing skeletal muscle cellular heterogeneity during development and aging.Our study could provide new targets and ideas for developing drugs to inhibit skeletal muscle aging and treat skeletal muscle diseases.展开更多
Background Myocardial infarction results in tissue necrosis, leading to cell loss and ultimately to cardiac failure. Implantation of skeletal muscle satellite cells into the scar area may compensate for the cell loss ...Background Myocardial infarction results in tissue necrosis, leading to cell loss and ultimately to cardiac failure. Implantation of skeletal muscle satellite cells into the scar area may compensate for the cell loss and provides a new strategy for infarct therapy. Vascular endothelial growth factor (VEGF) is a promising reagent for inducing myocardial angiogenesis. Skeletal myoblast transplantation has been shown to improve cardiac function in chronic heart failure models by regenerating muscle. We hypothesized that VEGF expression and vascular regeneration increased in infarcted myocardium by skeletal muscle satellite cells, which can promote vascular producing and improve survival environment in infarcted myocardium. Methods The skeletal muscle satellite cells were implanted into the infarcted myocardium in a model through ligated left anterior artery in Louis Inbrad Strain rat. Specimens were got for identifying the expression of VEGF and the density of vascular by immunochemical method at two weeks after implantation. Results The proliferation and differentiation of the skeletal muscle satellite cell was very well. The expression of VEGF was higher in the implanted group (146.83±2.49) than that in the control group (134.26±6.84) (P〈0.05). The vascular density in the implanted group (13,00± 1.51) was also higher than that in the control (10.68 ± 1.79) (P〈0.05). Conclusion The implanted satellite cell could excrete growth factor that would induce angiogenesis and improve cell survival environment in infarcted myocardium.展开更多
Objective: To study the mechanism of Tuina in the treatment of skeletal muscle injury. Methods: Rabbits were heavily beaten at gastrocnemius muscle to make acute contusion model and then treated respectively by earl...Objective: To study the mechanism of Tuina in the treatment of skeletal muscle injury. Methods: Rabbits were heavily beaten at gastrocnemius muscle to make acute contusion model and then treated respectively by early Tuina and routine Tuina. The number of satellite cells of skeletal muscles was observed. Results: The number of the satellite cells continued to grow in both groups, and it began to increase significantly 3-5 days after Tuina treatment. Early Tuina treatment produces larger number of satellite cells than routine Tuina treatment. Conclusion: Early Tuina treatment is helpful to the marked recovery of skeletal muscles by increasing the number of satellite cell.展开更多
Objective To study the effects of skeletal muscle satellite cells implanted into infarcted myocardium on the volume of remnant myocytes Methods Thirty six adult mongrel canines were divided randomly into implantat...Objective To study the effects of skeletal muscle satellite cells implanted into infarcted myocardium on the volume of remnant myocytes Methods Thirty six adult mongrel canines were divided randomly into implantation group and control group In the implantation group, skeletal muscle satellite cells taken from the gluteus maximus muscles of the dogs were cultured, proliferated and labeled with 4', 6 diamidino 2 phenylindone (DAPI) in vitro In both groups, a model of acute myocardial infarction was established in every dog In the implantation group, each dog was injected with M199 solution containing autologous skeletal muscle satellite cells The dogs in the control group received M199 solution without skeletal muscle satellite cells The dogs of both groups were killed 2, 4 and 8 weeks after implantation (six dogs in a separate group each time) Both infarcted myocardium and normal myocytes distal from the infracted regions isolated were observed under optical and fluorescent microscope Their volumes were determined using a confocal microscopy image analysis system and analyzed using SAS A P <0 05 was considered significant Results A portion of the implanted cells differentiated into muscle fiber with striations and were connected with intercalated discs Cross sectional area and cell volume were increased in normal myocardium Hypertrophy of remnant myocytes in the infarcted site after skeletal muscle cell implantation was much more evident than in the control group. Cross sectional area, cell area and cell volume differed significantly from those of the control group ( P < 0.05) Hypertrophy of the cells occurred predominantly in terms of width and thickness, whereas cell length remained unchanged Conclusion Skeletal muscle satellite cells implanted into infarct myocardium, could induce the hypertrophy of remnant myocyte cells in the infarcted site and could also aid in the recovery of the contractile force of the infarcted myocardium展开更多
Background:Electrical stimulation has been recommended as an effective therapy to prevent muscle atrophy after nerve injury.However,the effect of electrical stimulation on the proliferation of satellite cells in dener...Background:Electrical stimulation has been recommended as an effective therapy to prevent muscle atrophy after nerve injury.However,the effect of electrical stimulation on the proliferation of satellite cells in denervated muscles has not yet been fully elucidated.This study was aimed to evaluate the changes in satellite cell proliferation after electrical stimulation in nerve injury and to determine whether these changes are related to the restoration of myofiber cross-section area(CSA).Methods:Sciatic nerve crush injury was performed in 48 male Sprague-Dawley rats.In half(24/48)of the rats,the gastrocnemius was electrically stimulated transcutaneously on a daily basis after injury,while the other half were not stimulated.Another group of 24 male Sprague-Dawley rats were used as sham operation controls without injury or stimulation.The rats were euthanized 2,4,and 6 weeks later.After 5-bromo-2’-deoxyuridine(BrdU)labeling,the gastrocnemia were harvested for the detection of paired box protein 7(Pax7),BrdU,myofiber CSA,and myonuclei number per fiber.All data were analyzed using two-way analysis of variance and Bonferroni post-hoc test.Results:The percentages of Pax7-positive nuclei(10.81±0.56%)and BrdU-positive nuclei(34.29±3.87%)in stimulated muscles were significantly higher compared to those in non-stimulated muscles(2.58±0.33%and 1.30±0.09%,respectively,Bonferroni t=15.91 and 18.14,P<0.05).The numbers of myonuclei per fiber(2.19±0.24)and myofiber CSA(1906.86±116.51 mm2)were also increased in the stimulated muscles(Bonferroni t=3.57 and 2.73,P<0.05),and both were positively correlated with the Pax7-positive satellite cell content(R2=0.52 and 0.60,P<0.01).There was no significant difference in the ratio of myofiber CSA/myonuclei number per fiber among the three groups.Conclusions:Our results indicate that satellite cell proliferation is promoted by electrical stimulation after nerve injury,which may be correlated with an increase in myonuclei number and myofiber CSA.展开更多
Adult skeletal muscle stem cells,also known satellite cells(SCs),are a highly heterogeneous population and reside between the basal lamina and the muscle fiber sarcolemma.Myofibers function as an immediate niche to su...Adult skeletal muscle stem cells,also known satellite cells(SCs),are a highly heterogeneous population and reside between the basal lamina and the muscle fiber sarcolemma.Myofibers function as an immediate niche to support SC self-renewal and activation during muscle growth and regeneration.Herein,we demonstrate that microRNA 378(miR-378)regulates glycolytic metabolism in skeletal muscle fibers,as evidenced by analysis of myofiber-specific miR-378 transgenic mice(TG).Subsequently,we evaluate SC function and muscle regeneration using miR-378 TG mice.We demonstrate that miR-378 TG mice significantly attenuate muscle regeneration because of the delayed activation and differentiation of SCs.Furthermore,we show that the miR-378-mediated metabolic switch enriches Pax7^(Hi) SCs,accounting for impaired muscle regeneration in miR-378 TG mice.Mechanistically,our data suggest that miR-378 targets the Akt1/FoxO1 pathway,which contributes the enrichment of Pax7^(Hi) SCs in miR-378 TG mice.Together,our findings indicate that miR-378 is a target that links fiber metabolism to muscle stem cell heterogeneity and provide a genetic model to approve the metabolic niche role of myofibers in regulating muscle stem cell behavior and function.展开更多
文摘Sarcopenia,or muscle loss,has been one of the hot topics in the medical field in recent years.Due to limited attention and effective treatments for sarcopenia in the past,many patients,especially the elderly,suffered irreversible damage to their motor function caused by sarcopenia.However,recent scientific studies have found that the occurrence and development of sarcopenia are closely related to the function and quantity of muscle satellite cells.This article briefly discusses the relationship between muscle satellite cells and sarcopenia.
文摘As the only source of stem cells, satellite cells play and extraordinary role in the remediation process of skeletal muscle after injury. This paper overviewed the biological characteristic of skeletal muscle satellite cells and its role in repairing muscle injury, and put forward the prospects of its application in muscle trauma repair.
基金supports of the grants from the Ministry of Science and Technology of China and the Department of Science and Tech-nology of Guangdong Province, Chinasupported by the National Basic Research Program of China (973 Program, 2004CB117500)the Earmarked Fund for Modern Agro-Industry Technology Research System, China
文摘A synthetic isoflavone (ISO-S) or genistein was added in culture medium at different concentrations (0, 10, 20, 30, 40, and 80 p.mol L^-1) to investigate the effects of soybean isoflavones on antioxidative capacity of porcine skeletal muscle satellite cells. After 48 h incubation, the suspension was cryopreserved for the determination of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-Px) activities, and malondialdehyde (MDA) content. The mRNA levels of SOD, CAT, and GSH-Px gene in cells were detected with Taqman fluorescent probe method. The results showed that the content of MDA and the activities and the mRNA levels of SOD of porcine skeletal muscle satellite cells were influenced by supplemented soybean isoflavone (P〈0.05) when adding 10-80 μmol L^-1 ISO-S or genistein in the medium. The MDA contents, SOD and CAT activities and their mRNA expression levels of porcine skeletal muscle cells responded quadratically (P〈 0.05) as the level of ISO-S or genistein increased. Pre-incubation of porcine skeletal muscle satellite cells with ISO-S or genistein at 10-40 pmol L-1 elevated the activities and the mRNA expression levels of SOD and CAT in cells concurrently and decreased the cellular content of MDA (P〈 0.05). The results indicated that pre-incubation of ISO-S or genistein at 10- 40μmol L^-1 could improve the antioxidative capacity of porcine skeletal muscle satellite cells.
基金supported by the Key Foundation for Basic and Application Research in Higher Education of guangdong, China (2017KZDXM009)the China Postdoctoral Science Foundation (2018M640789)the Provincial Agricultural Science Innovation and Promotion Project, China. (2018LM2150)
文摘Pig is an important economic animal in China. Improving meat quality and meat productivity is a long time issue in animal genetic breeding. Micro RNAs(mi RNAs) are short non-coding RNAs that participate in various biological processes, such as muscle development and embryogenesis. mi R-22 differentially expresses in embryonic and adult skeletal muscle. However, the underlying mechanism is unclear. In this study, we investigated mi R-22 function in proliferation and differentiation of porcine satellite cells(PSCs) in skeletal muscle. Our data show that mi R-22 expressed in both proliferation and differentiated PSCs and is significantly upregulated(P<0.05) during differentiation. After treated with the mi R-22 inhibitor, PSCs proliferation was significantly increased(P<0.05), as indicated by the up-regulation(P<0.01) of cyclin D1(CCND1), cyclin B1(CCNB1) and down-regulation(P<0.05) of P21. Conversely, over-expression of mi R-22 resulted in opposite results. Differentiation of PSCs was significantly suppressed(P<0.05), evidenced by two major myogenic markers: myogenin(Myo G) and myosin heavy chain(My HC), after transfecting the PSCs with mi R-22 inhibitor. Opposite results were demonstrated in the other way around by transfection with mi R-22 mimics. In conclusion, the data from this study indicated that mi R-22 inhibited the PSCs proliferation but promoted their differentiation.
基金supported by the National Natural Science Foundation of China(81770950,81970841)Chinese Academy of Medical Sciences(CAMS)Innovation Fund for Medical Sciences(2019-12M-5-032)Department of Science and Technology of Sichuan Province(21ZDYF4279,2020JDZH0026,2021JDZH0022)。
文摘Phosphatidylserine(PS)is distributed asymmetrically in the plasma membrane of eukaryotic cells.Phosphatidylserine flippase(P4-ATPase)transports PS from the outer leaflet of the lipid bilayer to the inner leaflet of the membrane to maintain PS asymmetry.TheβsubunitTMEM30 Ais indispensable for transport and proper function of P4-ATPase.Previous studies have shown that the ATP11 A and TMEM30 A complex is the molecular switch for myotube formation.However,the role of Tmem30 a in skeletal muscle regeneration remains elusive.In the current study,Tmem30 a was highly expressed in the tibialis anterior(TA)muscles of dystrophin-null(mdx)mice and BaCl2-induced muscle injury model mice.We generated a satellite cell(SC)-specific Tmem30 a conditional knockout(cKO)mouse model to investigate the role of Tmem30 a in skeletal muscle regeneration.The regenerative ability of cKO mice was evaluated by analyzing the number and diameter of regenerated SCs after the TA muscles were injured by BaCl2-injection.Compared to the control mice,the cKO mice showed decreased Pax7+and MYH3+SCs,indicating diminished SC proliferation,and decreased expression of muscular regulatory factors(MYOD and MYOG),suggesting impaired myoblast proliferation in skeletal muscle regeneration.Taken together,these results demonstrate the essential role of Tmem30 a in skeletal muscle regeneration.
基金Supported by the Ministry of Agricultural Nuarture of New Varieties Genetically Modified Organisms Significant Special Funding (2008ZX08007-002)
文摘To examine the effect of myogenin gene on the differentiation of bovine skeletal muscle satellite cell, we constructed small interfering RNA plasmid vector to obtain myogenin knockdown bovine skeletal muscle cells, then used cell transfection, real time RCR and Western Blot to detect the influence of myogenin to cell differentiation. Results showed that the knockdown of myogenin significantly decreased its expression and other muscle-specific genes. Compared to the control, it could differentiate into few myotubes when challenged by low serum in the medium. These findings provided an important theoretical basis for further explore of the genetic mechanism in adult skeletal muscle, the remedy of muscle injuries and the cultivation of high-yield transgenic cattle.
基金supported by the National Nature Science Foundation of China (Project No. U0931004)the Sino-German Cooperation in Agriculture (Project No. 28/04-05CHN7 2010–2011)
文摘Background: Muscle growth depends on the fusion of proliferate satellite cells to existing myofibers. We reported previously that 0-14 day intermittent feeding led to persistent retardation in myofiber hypertrophy. However, how satellite cells respond to such nutritional insult has not been adequately elucidated. Results: One-day-old broiler chicks were allocated to control (Con, ad libitum feeding), intermittent feeding (IF, feed provided on alternate days) and re-feeding (RF, 2 days ad libitum feeding after 12 days of intermittent feeding) groups. Chickens were killed on Day 15 and satellite cells were isolated. When cultured, satellite cells from the IF group demonstrated significant retardation in proliferation and differentiation potential, while RF partly restored the proliferation rate and differentiation potential of the satellite cells. Significant up-regulation of insulin like growth factor I receptor (IGF-IR) (P〈O.05) and thyroid hormone receptor o (TRo) (P〈O.05), and down-regulation of growth hormone receptor (GHR) (P〈O.01) and IGF-I (P〈O.01) mRNA expression was observed in freshly isolated IF satellite cells when compared with Con cells. In RF cells, the mRNA expression of IGF-I was higher (P〈O.05) and of TRa was lower (P〈O.01) than in IF cells, suggesting that RF restored the mRNA expression of TRa and IGF-I, but not of GHR and IGF-IR. The Bax/Bcl-2 ratio tended to increase in the IF group, which was reversed in the RF group (P〈O.05), indicating that RF reduced the pro-apoptotic influence of iF. Moreover, no significant effect of T3 was detected on cell survival in IF cells compared with Con (P〈O.O01) or RF (P〈O.05) cells. Conclusions: These data suggest that early-age feed restriction inhibits the proliferation and differentiation of satellite cells, induces changes in mRNA expression of the GH/IGF-I and thyroid hormone receptors in satellite cells, as well as blunted sensitivity of satellite cells to T3, and that RF partially reverses these effects. Thus, a moderate nutritional strategy for feed restriction should be chosen in early chick rearing systems.
文摘Numerous physiological and pathological processes are controlled by free fatty acids, which act as signaling molecules in mammals. We hypothesized that oleic acid (Ole) might stimulate the formation of satellite-cell-derived intramuscular adipose tissue. The role of Ole as a ligand of <em>G-protein-coupled receptor 43</em> (<em>GPR4</em>3) was previously identified. Thus, the objective of the current study was to determine the effect of Ole on <em>GPR43</em> and factors related to the adipogenic differentiation of bovine satellite cells (BSC). Treatments of 100 μM and 500 μM Ole tended to induce greater (P < 0.10) mRNA expression of <em>CCAAT/enhancer-binding protein β</em> (<em>C/EBPβ</em>) compared to all other doses. The mRNA abundance of peroxisome proliferator-activated receptor γ (<em>PPARγ</em>) was not altered (<em>P</em> > 0.10) by treatment. The addition of 100 μM and 500 μM of Ole upregulated (<em>P</em> < 0.05) <em>GPR43</em> mRNA expression. Protein level of GPR43 was increased (<em>P</em> < 0.05) by 100 μM of Ole treatments. Addition of Ole to BSC cultures induced transformation of myogenic cells into adipocyte-like cells that formed cytoplasmic lipid droplets. Increased expression of<em> C/EBPβ</em> in response to Ole might suppress myogenic differentiation. After the treatment of cells with Ole, increased expression of GPR43 could lead to phosphorylation of 5’ AMP-activated protein kinase α (AMPKα). Altogether, the results indicated that increased Ole might stimulate adipose tissue accumulation within the skeletal muscle of cattle by promoting adipogenic differentiation and activation of GPR43 in satellite cells.
基金supported by grants from the Special Doctor Program of Nantong University(No.05024276)the Outstanding Teacher Program of Nantong University(No.03080542)
文摘This study investigated the protective effect of ATP on skeletal muscle satellite cells damaged by H2O2 in neonatal rats and the possible mechanism. The skeletal muscle satellite cells were randomly divided into four groups: normal group, model group(cells treated with 0.1 mmol/L H2O2 for 50 s), protection group(cells treated with 16, 8, 4, 2, 1, 0.5, or 0.25 mmol/L ATP for 24 h, and then with 0.1 mmol/L H2O2 for 50 s), proliferation group(cells treated with 16, 8, 4, 2, 1, 0.5, or 0.25 mmol/L ATP for 24 h). MTT assay, FITC+PI+DAPI fluorescent staining, Giemsa staining and immunofluorescence were performed to examine cell viability and apoptosis, and apoptosis-related proteins. The results showed that the survival rate of skeletal muscle satellite cells was decreased and the apoptosis rate was increased after H2O2 treatment(P〈0.01). Different doses of ATP had different effects on skeletal muscle satellite cells damaged by H2O2: the survival rate of muscle satellite cells treated with ATP at 4, 2, or 1 mmol/L was increased. The protective effect was most profound on cells treated with 2 mmol/L ATP. Immunofluorescence showed that ATP could increase the number of Bcl-2-positive cells(P〈0.01) and decrease the number of the Bax-positive cells(P〈0.01). It was concluded that ATP could protect skeletal muscle satellite cells against H2O2 damage in neonatal rats, which may be attributed to the up-regulation of the expression of Bcl-2 and down-regulation of Bax, resulting in the suppression of apoptosis.
基金Supported by grants from the Nature Science Foundation of China(39770735)
文摘Objective To study the cell growth factor secretion and vascular regeneration in acute in-farcted myocardium after autologous skeletal muscle satellite cell implantation. Methods Autologous skeletal muscle satellite cells from adult mongrel canine were implanted into the acute myocardial infarct site via the ligated left anterior descending (LAD) artery. Specimens were harvested at 2, 4 , 8 weeks after implantation for the expression of insulin-like growth factor-1 (IGF-1), basic fibroblast growth factor ( bFGF) and the vascular density. Results The expression of IGF-1, bFGF and the vascular density in skeletal muscle satellite cell implant group were higher than that in the control group. Conclusion The skeletal muscle satellite cells, after being implanted into the acute myocardial infarction, not only showed myocardial regeneration, but also showed the ability to secrete the cell factors, hence representing a positive effect on the regeneration of the infarcted myocardium.
文摘Objective To study the improvement of infarcted myocardial contractile force after autologous skeletal muscle satellite cell implantation via intracoronary arterial perfusion. Methods Skeletal muscle cells were harvested from gluteus max of adult mongrel dogs and the cells were cultured and expanded before being labeled with DAPI (4’, 6-diamidino-2-phenylindone). The labeled cells were then implanted into the acute myocardial infarct site via the ligated left anterior descending (LAD) coronary artery. Specimens were taken at 2nd, 4th, 8th week after myoblast implantation for histologic and contractile force evaluation, respectively. Results The satellite cells with fluorescence had been observed in the infarct site and also in papi- llary muscle with consistent oriented direction of host myocardium. A portion of the implanted cells had differen- tiated into muscle fibers. Two weeks after implantation, the myocardial contractile force showed no significant difference between the cell implant group and control group. At 4 and 8 week, the contractile force in the cell implant group was better than that in control group. Conclusion The skeletal muscle satellite cells, implanted into infarct myocardium by intracoronary arterial perfusion, could disseminate through the entire infarcted zone with myocardial regeneration and improve the contractile function of the infarcted myocardium.
基金supported by the Guangdong Basic and Applied Basic Research Foundation(2020B1515020046)“GDAS”Project of Science and Technology Development(2021GDASYL20210102003,2018GDASCX-0102)+4 种基金the National Natural Science Foundation of China(82072436,32130099)Open Program of Guangdong Provincial Key Laboratory of Medical Molecular Diagnostics(GPKLMMD-OP202102)Outstanding Youth Fund of Hunan Natural Science Foundation(2021JJ20045)the Outstanding Youth Fund of Hunan Natural Science Foundation(2021JJ20045)Youth Innovation Promotion Association of Chinese Academy of Sciences(2022370)。
文摘The gut microbiota plays a pivotal role in systemic metabolic processes and in particular functions,such as developing and preserving the skeletal muscle system.However,the interplay between gut microbiota/metabolites and the regulation of satellite cell(SC)homeostasis,particularly during aging,remains elusive.We propose that gut microbiota and its metabolites modulate SC physiology and homeostasis throughout skeletal muscle development,regeneration,and aging process.Our investigation reveals that microbial dysbiosis manipulated by either antibiotic treatment or fecal microbiota transplantation from aged to adult mice,leads to the activation of SCs or a significant reduction in the total number.Furthermore,employing multi-omics(e.g.,RNA-seq,16S r RNA gene sequencing,and metabolomics)and bioinformatic analysis,we demonstrate that the reduced butyrate levels,alongside the gut microbial dysbiosis,could be the primary factor contributing to the reduction in the number of SCs and subsequent impairments during skeletal muscle aging.Meanwhile,butyrate supplementation can mitigate the antibiotics-induced SC activation irrespective of gut microbiota,potentially by inhibiting the proliferation and differentiation of SCs/myoblasts.The butyrate effect is likely facilitated through the monocarboxylate transporter 1(Mct1),a lactate transporter enriched on membranes of SCs and myoblasts.As a result,butyrate could serve as an alternative strategy to enhance SC homeostasis and function during skeletal muscle aging.Our findings shed light on the potential application of microbial metabolites in maintaining SC homeostasis and preventing skeletal muscle aging.
基金supported by the National Natural Science Foundation of China,No.82173796(to CX)the Research Project of Zhejiang Chinese Medical University,No.2022JKJNTZ13(to XQ).
文摘Satellite glial cells are unique glial cells that surround the cell body of primary sensory neurons.An increasing body of evidence suggests that in the presence of inflammation and nerve damage,a significant number of satellite glial cells become activated,thus triggering a series of functional changes.This suggests that satellite glial cells are closely related to the occurrence of chronic pain.In this review,we first summarize the morphological structure,molecular markers,and physiological functions of satellite glial cells.Then,we clarify the multiple key roles of satellite glial cells in chronic pain,including gap junction hemichannel Cx43,membrane channel Pannexin1,K channel subunit 4.1,ATP,purinergic P2 receptors,and a series of additional factors and their receptors,including tumor necrosis factor,glutamate,endothelin,and bradykinin.Finally,we propose that future research should focus on the specific sorting of satellite glial cells,and identify genomic differences between physiological and pathological conditions.This review provides an important perspective for clarifying mechanisms underlying the peripheral regulation of chronic pain and will facilitate the formulation of new treatment plans for chronic pain.
基金supported by the Shenzhen Fundamental Research Program,China(No.JCYJ20180306173518936)Sanming Project of Medicine in Shenzhen,China(No.SZSM201612055)+1 种基金HKU-SZH Fund for Shenzhen Key Medical Discipline(China)(No.SZXK2020084)China National GeneBank(CNGB).
文摘To uncover the role of satellite cells(SCs)in paravertebral muscle development and aging,we constructed a single-nucleus transcriptomic atlas of mouse paravertebral muscle across seven timepoints spanning the embryo(day 16.5)to old(month 24)stages.Eight cell types,including SCs,fast muscle cells,and slow muscle cells,were identified.An energy metabolism-related gene set,TCA CYCLE IN SENESCENCE,was enriched in SCs.Forty-two skeletal muscle disease-related genes were highly expressed in SCs and exhibited similar expression patterns.Among them,Pdha1 was the core gene in the TCA CYCLE IN SENESCENCE;Pgam2,Sod1,and Suclg1 are transcription factors closely associated with skeletal muscle energy metabolism.Transcription factor enrichment analysis of the 42 genes revealed that Myod1 and Mef2a were also highly expressed in SCs,which regulated Pdha1 expression and were associated with skeletal muscle development.These findings hint that energy metabolism may be pivotal in SCs development and aging.Three ligand-receptor pairs of extracellular matrix(ECM)-receptor interactions,Lamc1-Dag1,Lama2-Dag1,and Hspg2-Dag1,may play a vital role in SCs interactions with slow/fast muscle cells and SCs self-renewal.Finally,we built the first database of a skeletal muscle single-cell transcriptome,the Musculoskeletal Cell Atlas(http://www.mskca.tech),which lists 630,040 skeletal muscle cells and provides interactive visualization,a useful resource for revealing skeletal muscle cellular heterogeneity during development and aging.Our study could provide new targets and ideas for developing drugs to inhibit skeletal muscle aging and treat skeletal muscle diseases.
基金This study was supported by a grant from the Natural Science Foundation of Hubei Province (No. 2004AB135).
文摘Background Myocardial infarction results in tissue necrosis, leading to cell loss and ultimately to cardiac failure. Implantation of skeletal muscle satellite cells into the scar area may compensate for the cell loss and provides a new strategy for infarct therapy. Vascular endothelial growth factor (VEGF) is a promising reagent for inducing myocardial angiogenesis. Skeletal myoblast transplantation has been shown to improve cardiac function in chronic heart failure models by regenerating muscle. We hypothesized that VEGF expression and vascular regeneration increased in infarcted myocardium by skeletal muscle satellite cells, which can promote vascular producing and improve survival environment in infarcted myocardium. Methods The skeletal muscle satellite cells were implanted into the infarcted myocardium in a model through ligated left anterior artery in Louis Inbrad Strain rat. Specimens were got for identifying the expression of VEGF and the density of vascular by immunochemical method at two weeks after implantation. Results The proliferation and differentiation of the skeletal muscle satellite cell was very well. The expression of VEGF was higher in the implanted group (146.83±2.49) than that in the control group (134.26±6.84) (P〈0.05). The vascular density in the implanted group (13,00± 1.51) was also higher than that in the control (10.68 ± 1.79) (P〈0.05). Conclusion The implanted satellite cell could excrete growth factor that would induce angiogenesis and improve cell survival environment in infarcted myocardium.
文摘Objective: To study the mechanism of Tuina in the treatment of skeletal muscle injury. Methods: Rabbits were heavily beaten at gastrocnemius muscle to make acute contusion model and then treated respectively by early Tuina and routine Tuina. The number of satellite cells of skeletal muscles was observed. Results: The number of the satellite cells continued to grow in both groups, and it began to increase significantly 3-5 days after Tuina treatment. Early Tuina treatment produces larger number of satellite cells than routine Tuina treatment. Conclusion: Early Tuina treatment is helpful to the marked recovery of skeletal muscles by increasing the number of satellite cell.
基金grantsfromtheNationalNaturalScienceFoundationofChina (No .3 9770 73 5 )
文摘Objective To study the effects of skeletal muscle satellite cells implanted into infarcted myocardium on the volume of remnant myocytes Methods Thirty six adult mongrel canines were divided randomly into implantation group and control group In the implantation group, skeletal muscle satellite cells taken from the gluteus maximus muscles of the dogs were cultured, proliferated and labeled with 4', 6 diamidino 2 phenylindone (DAPI) in vitro In both groups, a model of acute myocardial infarction was established in every dog In the implantation group, each dog was injected with M199 solution containing autologous skeletal muscle satellite cells The dogs in the control group received M199 solution without skeletal muscle satellite cells The dogs of both groups were killed 2, 4 and 8 weeks after implantation (six dogs in a separate group each time) Both infarcted myocardium and normal myocytes distal from the infracted regions isolated were observed under optical and fluorescent microscope Their volumes were determined using a confocal microscopy image analysis system and analyzed using SAS A P <0 05 was considered significant Results A portion of the implanted cells differentiated into muscle fiber with striations and were connected with intercalated discs Cross sectional area and cell volume were increased in normal myocardium Hypertrophy of remnant myocytes in the infarcted site after skeletal muscle cell implantation was much more evident than in the control group. Cross sectional area, cell area and cell volume differed significantly from those of the control group ( P < 0.05) Hypertrophy of the cells occurred predominantly in terms of width and thickness, whereas cell length remained unchanged Conclusion Skeletal muscle satellite cells implanted into infarct myocardium, could induce the hypertrophy of remnant myocyte cells in the infarcted site and could also aid in the recovery of the contractile force of the infarcted myocardium
基金Supported by the grants from the National Natural Science Foundation of China(No.81501940,No.11472018,No.81871851).
文摘Background:Electrical stimulation has been recommended as an effective therapy to prevent muscle atrophy after nerve injury.However,the effect of electrical stimulation on the proliferation of satellite cells in denervated muscles has not yet been fully elucidated.This study was aimed to evaluate the changes in satellite cell proliferation after electrical stimulation in nerve injury and to determine whether these changes are related to the restoration of myofiber cross-section area(CSA).Methods:Sciatic nerve crush injury was performed in 48 male Sprague-Dawley rats.In half(24/48)of the rats,the gastrocnemius was electrically stimulated transcutaneously on a daily basis after injury,while the other half were not stimulated.Another group of 24 male Sprague-Dawley rats were used as sham operation controls without injury or stimulation.The rats were euthanized 2,4,and 6 weeks later.After 5-bromo-2’-deoxyuridine(BrdU)labeling,the gastrocnemia were harvested for the detection of paired box protein 7(Pax7),BrdU,myofiber CSA,and myonuclei number per fiber.All data were analyzed using two-way analysis of variance and Bonferroni post-hoc test.Results:The percentages of Pax7-positive nuclei(10.81±0.56%)and BrdU-positive nuclei(34.29±3.87%)in stimulated muscles were significantly higher compared to those in non-stimulated muscles(2.58±0.33%and 1.30±0.09%,respectively,Bonferroni t=15.91 and 18.14,P<0.05).The numbers of myonuclei per fiber(2.19±0.24)and myofiber CSA(1906.86±116.51 mm2)were also increased in the stimulated muscles(Bonferroni t=3.57 and 2.73,P<0.05),and both were positively correlated with the Pax7-positive satellite cell content(R2=0.52 and 0.60,P<0.01).There was no significant difference in the ratio of myofiber CSA/myonuclei number per fiber among the three groups.Conclusions:Our results indicate that satellite cell proliferation is promoted by electrical stimulation after nerve injury,which may be correlated with an increase in myonuclei number and myofiber CSA.
基金This work was supported by grants from the National Natural Science Foundation of China(91949106,31971080 and 32000603)the Natural Science Foundation of Beijing(7192125).
文摘Adult skeletal muscle stem cells,also known satellite cells(SCs),are a highly heterogeneous population and reside between the basal lamina and the muscle fiber sarcolemma.Myofibers function as an immediate niche to support SC self-renewal and activation during muscle growth and regeneration.Herein,we demonstrate that microRNA 378(miR-378)regulates glycolytic metabolism in skeletal muscle fibers,as evidenced by analysis of myofiber-specific miR-378 transgenic mice(TG).Subsequently,we evaluate SC function and muscle regeneration using miR-378 TG mice.We demonstrate that miR-378 TG mice significantly attenuate muscle regeneration because of the delayed activation and differentiation of SCs.Furthermore,we show that the miR-378-mediated metabolic switch enriches Pax7^(Hi) SCs,accounting for impaired muscle regeneration in miR-378 TG mice.Mechanistically,our data suggest that miR-378 targets the Akt1/FoxO1 pathway,which contributes the enrichment of Pax7^(Hi) SCs in miR-378 TG mice.Together,our findings indicate that miR-378 is a target that links fiber metabolism to muscle stem cell heterogeneity and provide a genetic model to approve the metabolic niche role of myofibers in regulating muscle stem cell behavior and function.