Spodoptera frugiperda is a highly destructive pest that has become a global problem due to its robust reproductive and migratory capabilities.Transient receptor potential(TRP)channels,which constitute a vast ion chann...Spodoptera frugiperda is a highly destructive pest that has become a global problem due to its robust reproductive and migratory capabilities.Transient receptor potential(TRP)channels,which constitute a vast ion channel family,play pivotal roles in sensing the external environment and maintaining internal homeostasis in insects.TRP channels have been widely investigated for their critical roles in regulating various insect behaviors in recent years.In this study,we identified 15 TRP gene loci encoding 26 transcripts in the genome of S.frugiperda and analyzed their expression profiles at different developmental stages.The results revealed that S.frugiperda possesses four TRPC genes,six TRPA genes,one TRPM gene,two TRPV genes,one TRPN gene,and one TRPML gene,while a canonical TRPP is absent.Moreover,the SfruTRPA1 was functionally characterized using the Xenopus oocyte expression system.The results showed that SfruTRPA1 is activated by temperature increases from 20 to 45℃,and there is no significant desensitization after repeated stimuli within the same temperature range.Additionally,SfruTRPA1 is activated by certain natural chemicals,including allyl isothiocyanate(AITC)and cinnamaldehyde(CA).These findings provide valuable insights to the TRP genes in S.frugiperda.展开更多
The study titled“Transient receptor potential-related risk model predicts prognosis of hepatocellular carcinoma patients”is a significant contribution to hepatocellular carcinoma(HCC)research,highlighting the role o...The study titled“Transient receptor potential-related risk model predicts prognosis of hepatocellular carcinoma patients”is a significant contribution to hepatocellular carcinoma(HCC)research,highlighting the role of transient receptor potential(TRP)family genes in the disease’s progression and prognosis.Utilizing data from The Cancer Genome Atlas database,it establishes a new risk assessment model,emphasizing the interaction of TRP genes with tumor proliferation pathways,key metabolic reactions like retinol metabolism,and the tumor immune microenvironment.Notably,the overexpression of the TRPC1 gene in HCC correlates with poorer patient survival outcomes,suggesting its potential as a prognostic biomarker and a target for personalized therapy,particularly in strategies combining immunotherapy and anti-TRP agents.展开更多
●AIM:To explore whether autophagy functions as a cellular adaptation mechanism in lens epithelial cells(LECs)under hyperosmotic stress.●METHODS:LECs were treated with hyperosmotic stress at the concentration of 270,...●AIM:To explore whether autophagy functions as a cellular adaptation mechanism in lens epithelial cells(LECs)under hyperosmotic stress.●METHODS:LECs were treated with hyperosmotic stress at the concentration of 270,300,400,500,or 600 mOsm for 6,12,18,24h in vitro.Polymerase chain reaction(PCR)was employed for the mRNA expression of autophagyrelated genes,while Western blotting detected the targeted protein expression.The transfection of stub-RFP-sens-GFPLC3 autophagy-related double fluorescence lentivirus was conducted to detect the level of autophagy flux.Scanning electron microscopy was used to detect the existence of autolysosome.Short interfering RNA of autophagy-related gene(ATG)7,transient receptor potential vanilloid(TRPV)1 overexpression plasmid,related agonists and inhibitors were employed to their influence on autophagy related pathway.Flow cytometry was employed to test the apoptosis and intracellular Ca^(2+)level.Mitochondrial membrane potential was measured by JC-1 staining.The cell counting kit-8 assay was used to calculate the cellular viability.The wound healing assay was used to evaluate the wound closure rate.GraphPad 6.0 software was utilized to evaluate the data.●RESULTS:The hyperosmotic stress activated autophagy in a pressure-and time-dependent manner in LECs.Beclin 1 protein expression and conversion of LC3B II to LC3B I increased,whereas sequestosome-1(SQSTM1)protein expression decreased.Transient Ca^(2+)influx was stimulated caused by hyperosmotic stress,levels of mammalian target of rapamycin(mTOR)phosphorylation decreased,and the level of AMP-activated protein kinase(AMPK)phosphorylation increased in the early stage.Based on this evidence,autophagy activation through the Ca^(2+)-dependent AMPK/mTOR pathway might represent an adaptation process in LECs under hyperosmotic stress.Hyperosmotic stress decreased cellular viability and accelerated apoptosis in LECs and cellular migration decreased.Inhibition of autophagy by ATG7 knockdown had similar results.TRPV1 overexpression increased autophagy and might be crucial in the occurrence of autophagy promoted by hyperosmotic stress.●CONCLUSION:A combination of hyperosmotic stress and autophagy inhibition may be a promising approach to decrease the number of LECs in the capsular bag and pave the way for improving prevention of posterior capsular opacification and capsular fibrosis.展开更多
The transient receptor potential melastatin 2 is a calcium-permeable cation channel member of the TRP family. Also known as an oxidative stress-activated channel, the transient receptor potential melastatin 2 gating m...The transient receptor potential melastatin 2 is a calcium-permeable cation channel member of the TRP family. Also known as an oxidative stress-activated channel, the transient receptor potential melastatin 2 gating mechanism is dependent on reactive oxygen species. In pathological conditions, transient receptor potential melastatin 2 is overactivated, leading to a Ca~(2+) influx that alters cell homeostasis and promotes cell death. The role of transient receptor potential melastatin 2 in neurodegenerative diseases, including Alzheimer's disease and ischemia, has already been described and reviewed. However, data on transient receptor potential melastatin 2 involvement in Parkinson's disease pathology has emerged only in recent years and the issue lacks review studies that focus specifically on this topic. The present review aims to elucidate the role of the transient receptor potential melastatin 2 channel in Parkinson's disease by reviewing, summarizing, and discussing the in vitro, in vivo, and human studies published until August 2022. Here we describe fourteen studies that evaluated the transient receptor potential melastatin 2 channel in Parkinson's disease. The Parkinson's disease model used, transient receptor potential melastatin 2 antagonist and genetic approaches, and the main outcomes reported were discussed. The studies described transient receptor potential melastatin 2 activation and enhanced expression in different Parkinson's disease models. They also evidenced protective and restorative effects when using transient receptor potential melastatin 2 antagonists, knockout, or silencing. This review provides a literature overview and suggests where there is a need for more research. As a perspective point, this review shows evidence that supports transient receptor potential melastatin 2 as a pharmacological target for Parkinson's disease in the future.展开更多
BACKGROUND Members of the transient receptor potential(TRP)protein family shape oncogenic development,but the specific relevance of TRP-related genes in hepatocellular carcinoma(HCC)has yet to be defined.AIM To invest...BACKGROUND Members of the transient receptor potential(TRP)protein family shape oncogenic development,but the specific relevance of TRP-related genes in hepatocellular carcinoma(HCC)has yet to be defined.AIM To investigate the role of TRP genes in HCC,their association with HCC development and treatment was examined.METHODS HCC patient gene expression and clinical data were downloaded from The Cancer Genome Atlas database,and univariate and least absolute shrinkage and selection operator Cox regression models were employed to explore the TRP-related risk spectrum.Based on these analyses,clinically relevant TRP family genes were selected,and the association between the key TRP canonical type 1(TRPC1)gene and HCC patient prognosis was evaluated.RESULTS In total,28 TRP family genes were screened for clinical relevance,with multivariate analyses ultimately revealing three of these genes(TRPC1,TRP cation channel subfamily M member 2,and TRP cation channel subfamily M member 6)to be significantly associated with HCC patient prognosis(P<0.05).These genes were utilized to establish a TRP-related risk model.Patients were separated into low-and high-risk groups based on the expression of these genes,and high-risk patients exhibited a significantly poorer prognosis(P=0.001).Functional analyses highlighted pronounced differences in the immune status of patients in these two groups and associated enriched immune pathways.TRPC1 was identified as a candidate gene in this family worthy of further study,with HCC patients expressing higher TRPC1 levels exhibiting poorer survival outcomes.Consistently,quantitative,immunohistochemistry,and western blot analyses revealed increased TRPC1 expression in HCC.CONCLUSION These three TRP genes help determine HCC patient prognosis,providing insight into tumor immune status and immunological composition.These findings will help design combination therapies including immunotherapeutic and anti-TRP agents.展开更多
AIM To investigate the anti-fibrotic effects of the traditional oriental herbal medicine Daikenchuto(DKT) associated with transient receptor potential ankyrin 1(TRPA1) channels in intestinal myofibroblasts. METHODS In...AIM To investigate the anti-fibrotic effects of the traditional oriental herbal medicine Daikenchuto(DKT) associated with transient receptor potential ankyrin 1(TRPA1) channels in intestinal myofibroblasts. METHODS Inflammatory and fibrotic changes were detected in a2,4,6-trinitrobenzenesulfonic acid(TNBS) chronic colitis model of wild-type and TRPA1-knockout(TRPA1-KO) mice via pathological staining and immunoblotting analysis.Ca^(2+) imaging experiments examined the effects of DKT and its components/ingredients on intestinal myofibroblast(In Myo Fib) cell TRPA1 channel function.Profibrotic factors and transforming growth factor (TGF) -β1-associated signaling were tested in an In Myo Fib cell line by q PCR and immunoblotting experiments.Samples from non-stenotic and stenotic regions of the intestines of patients with Crohn’s disease (CD) were used for pathological analysis. RESULTS Chronic treatment with TNBS caused more severe inflammation and fibrotic changes in TRPA1-KO than in wild-type mice.A one-week enema administration of DKT reduced fibrotic lesions in wild-type but not in TRPA1-KO mice.The active ingredients of DKT,i.e.,hydroxyα-sanshool and 6-shogaol,induced Ca^(2+) influxes in In Myo Fib,and this was antagonized by co-treatment with a selective TRPA1 channel blocker,HC-030031.DKT counteracted TGF-β1-induced expression of TypeⅠcollagen andα-smooth muscle actin (α-SMA) ,which were accompanied by a reduction in the phosphorylation of Smad-2 and p38-mitogen-activated protein kinase (p38-MAPK) and the expression of myocardin.Importantly,24-h incubation with a DKT active component Japanese Pepper increased the m RNA and protein expression levels of TRPA1 in In Myo Fibs,which in turn negatively regulated collagen synthesis.In the stenotic regions of the intestines of CD patients,TRPA1 expression was significantly enhanced.CONCLUSION The effects of DKT on the expression and activation of the TRPA1 channel could be advantageous for suppressing intestinal fibrosis,and benefit inflammatory bowel disease treatment.展开更多
Transient receptor potential channel A1 is one of the important transducers of noxious stimuli in the primary afferents, which may contribute to generation of neurogenic inflammation and hyperalgesia. The present stud...Transient receptor potential channel A1 is one of the important transducers of noxious stimuli in the primary afferents, which may contribute to generation of neurogenic inflammation and hyperalgesia. The present study was designed to investigate if activation of transient receptor potential channel A1 may induce calcitonin gene-related peptide release from the primary afferent neurons. We found that application of allyl isothiocyanate, a transient receptor potential channel A1 activator, caused calcitonin gene-related peptide release from the cultured rat dorsal root ganglion neurons. Knock- down of transient receptor potential channel A1 with an antisense oligodeoxynucleotide prevented calcitonin gene-related peptide release by allyl isothiocyanate application in cultured dorsal root ganglion neurons. Thus, we concluded that transient receptor potential channel A1 activation caused calcitonin gene-related peptide release in sensory neurons.展开更多
The transient receptor potential cation channel subfamily V member 1（TRPV1） provides the sensation of pain（nociception）. However, it remains unknown whether TRPV1 is activated after peripheral nerve injury, or whe...The transient receptor potential cation channel subfamily V member 1（TRPV1） provides the sensation of pain（nociception）. However, it remains unknown whether TRPV1 is activated after peripheral nerve injury, or whether activation of TRPV1 affects neural regeneration. In the present study, we established rat models of unilateral sciatic nerve crush injury, with or without pretreatment with AMG517（300 mg/kg）, a TRPV1 antagonist, injected subcutaneously into the ipsilateral paw 60 minutes before injury. At 1 and 2 weeks after injury, we performed immunofluorescence staining of the sciatic nerve at the center of injury, at 0.3 cm proximal and distal to the injury site, and in the dorsal root ganglia. Our results showed that Wallerian degeneration occurred distal to the injury site, and neurite outgrowth and Schwann cell regeneration occurred proximal to the injury. The number of regenerating myelinated and unmyelinated nerve clusters was greater in the AMG517-pretreated rats than in the vehicle-treated group, most notably 2 weeks after injury. TRPV1 expression in the injured sciatic nerve and ipsilateral dorsal root ganglia was markedly greater than on the contralateral side. Pretreatment with AMG517 blocked this effect. These data indicate that TRPV1 is activated or overexpressed after sciatic nerve crush injury, and that blockade of TRPV1 may accelerate regeneration of the injured sciatic nerve.展开更多
BACKGROUND Transient receptor potential vanilloid-1(TRPV1),a nonselective cation channel,is activated by capsaicin,a pungent ingredient of hot pepper.Previous studies have suggested a link between obesity and capsaici...BACKGROUND Transient receptor potential vanilloid-1(TRPV1),a nonselective cation channel,is activated by capsaicin,a pungent ingredient of hot pepper.Previous studies have suggested a link between obesity and capsaicin-associated pathways,and activation of TRPV1 may provide an alternative approach for obesity treatment.However,data on the TRPV1 distribution in human gastric mucosa are limited,and the degree of TRPV1 distribution in the gastric and duodenal mucosal cells of obese people in comparison with normal-weight individuals is unknown.AIM To clarify gastric and duodenal mucosal expression of TRPV1 in humans and compare TRPV1 expression in obese and healthy individuals.METHODS Forty-six patients with a body mass index(BMI)of>40 kg/m^(2) and 20 patients with a BMI between 18-25 kg/m^(2) were included.Simultaneous biopsies from the fundus,antrum,and duodenum tissues were obtained from subjects between the ages of 18 and 65 who underwent esophagogastroduodenoscopy.Age,sex,history of alcohol and cigarette consumption,and past medical history regarding chronic diseases and medications were accessed from patient charts and were analyzed accordingly.Evaluation with anti-TRPV1 antibody was performed separately according to cell types in the fundus,antrum,and duodenum tissues using an immunoreactivity score.Data were analyzed using SPSS 17.0.RESULTS TRPV1 expression was higher in the stomach than in the duodenum and was predominantly found in parietal and chief cells of the fundus and mucous and foveolar cells of the antrum.Unlike foveolar cells in the antrum,TRPV1 was relatively low in foveolar cells in the fundus(4.92±0.49 vs 0.48±0.16,P<0.01,Mann-Whitney U test).Additionally,the mucous cells in the duodenum also had low levels of TRPV1 compared to mucous cells in the antrum(1.33±0.31 vs 2.95±0.46,P<0.01,Mann-Whitney U test).TRPV1 expression levels of different cell types in the fundus,antrum,and duodenum tissues of the morbidly obese group were similar to those of the control group.Staining with TRPV1 in fundus chief cells and antrum and duodenum mucous cells was higher in patients aged≥45 years than in patients<45 years(3.03±0.42,4.37±0.76,2.28±0.55 vs 1.9±0.46,1.58±0.44,0.37±0.18,P=0.03,P<0.01,P<0.01,respectively,Mann-Whitney U test).The mean staining levels of TRPV1 in duodenal mucous cells in patients with diabetes and hypertension were higher than those in patients without diabetes and hypertension(diabetes:2.11±0.67 vs 1.02±0.34,P=0.04;hypertension:2.42±0.75 vs 1.02±0.33,P<0.01 Mann-Whitney U test).CONCLUSION The expression of TRPV1 is unchanged in the gastroduodenal mucosa of morbidly obese patients demonstrating that drugs targeting TRPV1 may be effective in these patients.展开更多
Background: Transient receptor potential ankyrin (TRPA) 1 is known as a peripheral initiator of acute inflammation and hyperalgesia. However, its role in the facilitation of innate immune responses followed by resolut...Background: Transient receptor potential ankyrin (TRPA) 1 is known as a peripheral initiator of acute inflammation and hyperalgesia. However, its role in the facilitation of innate immune responses followed by resolution of the inflammation triggered by a surgical incision has not been fully investigated. Therefore, we evaluated the mechanism by which TRPA1 regulates the inflammatory responses mainly facilitated by neutrophils and macrophages in the early course of wound repair after an incision. Methods: Plantar incision was performed in wild-type and TRPA1-/- mice. The infiltration of polymorphonuclear neutrophils, macrophage phenotype, and induction of inflammatory mediators were assessed for 7 days postoperatively. Results: TRPA1-/-?mice exhibited decreased infiltration of polymorphonuclear neutrophilscompared with wild-type mice on day 1. Consistently, the influx of F4/80+ iNOS+ proinflammatory M1 macrophages to incised sites was markedly decreased on day 2. Similarly, F4/80+ CD206+M2 macrophages, which regulate the resolution of inflammation and promote wound healing in the later phase of acute inflammation, were significantly decreased in TRPA1-/- compared with those in wild-type mice on day 7. In addition, the induction of heme oxygenase-1, which promotes wound healing by switching phenotype of macrophages, was decreased in the early phase of acute inflammation, whereas the expression of proinflammatory mediators such as tumor necrosis factor and cyclooxygenase-2, and 15-lipoxygenase, which are involved in the resolution of inflammation was increased in the late phase in TRPA1-/- mice. Conclusions: Early innate immune responses including neutrophil infiltration and macrophage polarization at incised sites were inhibited in TRPA1-/- mice, associated with increased pro-inflammatory mediators in later phase. Peripheral TRPA1 may facilitate the acute inflammatory process, leading to the promotion of macrophage-mediated resolution of inflammation and wound repair after a surgical incision.展开更多
Background: It is important to maintain skin homeostasis for cosmetic and medical reasons. Many ceramide-related ingredients and cosmetics have been developed to improve the skin barrier function and skin hydration. S...Background: It is important to maintain skin homeostasis for cosmetic and medical reasons. Many ceramide-related ingredients and cosmetics have been developed to improve the skin barrier function and skin hydration. Similar to extracellular lipids, the cornified envelope, which is a structure formed beneath the plasma membrane, contributes to the skin barrier function as a scaffold for extracellular lipids. Therefore, in this study, we focused on transglutaminase 1 (TGM1) which is the key enzyme for formation of the cornified envelope Objective: The objectives of this study were to identify compounds that could upregulate the expression of TGM1 and evaluate their underlying action mechanisms. Methods: Expression of the transient receptor potential channel vanilloid subfamily member 4 (TRPV4) at the mRNA and protein levels was estimated by PCR and western blotting. Effects of baicalein and Salvia officinalis (SO) extract on TGM1 mRNA expression were measured by PCR. The involvement of TRPV4 in TGM1 mRNA expression was evaluated by the inhibition and silencing of TRPV4. Results: TRPV4 was expressed in both basal cell-like HaCaT cells and suprabasal cell-like HaCaT cells. Baicalein and SO extract upregulated TGM1 mRNA expression in basal cell-like HaCaT cells. However, inhibition and silencing of TRPV4 abrogated the effects of baicalein and SO extract. Conclusion: Baicalein and SO extract upregulated the expression of TGM1 mRNA via the activation of TRPV4, suggesting that it may improve the skin barrier function by enhancing cornified envelope formation.展开更多
基金funded by the Shenzhen Science and Technology Program,China(KQTD20180411143628272)the Special Funds for Science Technology Innovation and Industrial Development of Shenzhen Dapeng New District,China(pt202101-02)the National Key R&D Program of China(2022YFE0116500).
文摘Spodoptera frugiperda is a highly destructive pest that has become a global problem due to its robust reproductive and migratory capabilities.Transient receptor potential(TRP)channels,which constitute a vast ion channel family,play pivotal roles in sensing the external environment and maintaining internal homeostasis in insects.TRP channels have been widely investigated for their critical roles in regulating various insect behaviors in recent years.In this study,we identified 15 TRP gene loci encoding 26 transcripts in the genome of S.frugiperda and analyzed their expression profiles at different developmental stages.The results revealed that S.frugiperda possesses four TRPC genes,six TRPA genes,one TRPM gene,two TRPV genes,one TRPN gene,and one TRPML gene,while a canonical TRPP is absent.Moreover,the SfruTRPA1 was functionally characterized using the Xenopus oocyte expression system.The results showed that SfruTRPA1 is activated by temperature increases from 20 to 45℃,and there is no significant desensitization after repeated stimuli within the same temperature range.Additionally,SfruTRPA1 is activated by certain natural chemicals,including allyl isothiocyanate(AITC)and cinnamaldehyde(CA).These findings provide valuable insights to the TRP genes in S.frugiperda.
文摘The study titled“Transient receptor potential-related risk model predicts prognosis of hepatocellular carcinoma patients”is a significant contribution to hepatocellular carcinoma(HCC)research,highlighting the role of transient receptor potential(TRP)family genes in the disease’s progression and prognosis.Utilizing data from The Cancer Genome Atlas database,it establishes a new risk assessment model,emphasizing the interaction of TRP genes with tumor proliferation pathways,key metabolic reactions like retinol metabolism,and the tumor immune microenvironment.Notably,the overexpression of the TRPC1 gene in HCC correlates with poorer patient survival outcomes,suggesting its potential as a prognostic biomarker and a target for personalized therapy,particularly in strategies combining immunotherapy and anti-TRP agents.
文摘●AIM:To explore whether autophagy functions as a cellular adaptation mechanism in lens epithelial cells(LECs)under hyperosmotic stress.●METHODS:LECs were treated with hyperosmotic stress at the concentration of 270,300,400,500,or 600 mOsm for 6,12,18,24h in vitro.Polymerase chain reaction(PCR)was employed for the mRNA expression of autophagyrelated genes,while Western blotting detected the targeted protein expression.The transfection of stub-RFP-sens-GFPLC3 autophagy-related double fluorescence lentivirus was conducted to detect the level of autophagy flux.Scanning electron microscopy was used to detect the existence of autolysosome.Short interfering RNA of autophagy-related gene(ATG)7,transient receptor potential vanilloid(TRPV)1 overexpression plasmid,related agonists and inhibitors were employed to their influence on autophagy related pathway.Flow cytometry was employed to test the apoptosis and intracellular Ca^(2+)level.Mitochondrial membrane potential was measured by JC-1 staining.The cell counting kit-8 assay was used to calculate the cellular viability.The wound healing assay was used to evaluate the wound closure rate.GraphPad 6.0 software was utilized to evaluate the data.●RESULTS:The hyperosmotic stress activated autophagy in a pressure-and time-dependent manner in LECs.Beclin 1 protein expression and conversion of LC3B II to LC3B I increased,whereas sequestosome-1(SQSTM1)protein expression decreased.Transient Ca^(2+)influx was stimulated caused by hyperosmotic stress,levels of mammalian target of rapamycin(mTOR)phosphorylation decreased,and the level of AMP-activated protein kinase(AMPK)phosphorylation increased in the early stage.Based on this evidence,autophagy activation through the Ca^(2+)-dependent AMPK/mTOR pathway might represent an adaptation process in LECs under hyperosmotic stress.Hyperosmotic stress decreased cellular viability and accelerated apoptosis in LECs and cellular migration decreased.Inhibition of autophagy by ATG7 knockdown had similar results.TRPV1 overexpression increased autophagy and might be crucial in the occurrence of autophagy promoted by hyperosmotic stress.●CONCLUSION:A combination of hyperosmotic stress and autophagy inhibition may be a promising approach to decrease the number of LECs in the capsular bag and pave the way for improving prevention of posterior capsular opacification and capsular fibrosis.
基金funded by Coordination for the Improvement of Higher Education Personnel (CAPES,Brazil-Finance Code 001,to LRB)the S?o Paulo Research Foundation(FAPESP,Brazil,project#2018/07366-4)+1 种基金The National Council for Scientific and Technological Development (CNPq,Brazil,project#303006/2018-8,to LRB)a PhD fellowship from FAPESP under Grant Agreement No 2020/02109-3。
文摘The transient receptor potential melastatin 2 is a calcium-permeable cation channel member of the TRP family. Also known as an oxidative stress-activated channel, the transient receptor potential melastatin 2 gating mechanism is dependent on reactive oxygen species. In pathological conditions, transient receptor potential melastatin 2 is overactivated, leading to a Ca~(2+) influx that alters cell homeostasis and promotes cell death. The role of transient receptor potential melastatin 2 in neurodegenerative diseases, including Alzheimer's disease and ischemia, has already been described and reviewed. However, data on transient receptor potential melastatin 2 involvement in Parkinson's disease pathology has emerged only in recent years and the issue lacks review studies that focus specifically on this topic. The present review aims to elucidate the role of the transient receptor potential melastatin 2 channel in Parkinson's disease by reviewing, summarizing, and discussing the in vitro, in vivo, and human studies published until August 2022. Here we describe fourteen studies that evaluated the transient receptor potential melastatin 2 channel in Parkinson's disease. The Parkinson's disease model used, transient receptor potential melastatin 2 antagonist and genetic approaches, and the main outcomes reported were discussed. The studies described transient receptor potential melastatin 2 activation and enhanced expression in different Parkinson's disease models. They also evidenced protective and restorative effects when using transient receptor potential melastatin 2 antagonists, knockout, or silencing. This review provides a literature overview and suggests where there is a need for more research. As a perspective point, this review shows evidence that supports transient receptor potential melastatin 2 as a pharmacological target for Parkinson's disease in the future.
基金Supported by National Natural Science Foundation of China,No.82260535National Natural Science Foundation of Guizhou Medical University Hospital Incubation Program,No.gyfynsfc-2022-07.
文摘BACKGROUND Members of the transient receptor potential(TRP)protein family shape oncogenic development,but the specific relevance of TRP-related genes in hepatocellular carcinoma(HCC)has yet to be defined.AIM To investigate the role of TRP genes in HCC,their association with HCC development and treatment was examined.METHODS HCC patient gene expression and clinical data were downloaded from The Cancer Genome Atlas database,and univariate and least absolute shrinkage and selection operator Cox regression models were employed to explore the TRP-related risk spectrum.Based on these analyses,clinically relevant TRP family genes were selected,and the association between the key TRP canonical type 1(TRPC1)gene and HCC patient prognosis was evaluated.RESULTS In total,28 TRP family genes were screened for clinical relevance,with multivariate analyses ultimately revealing three of these genes(TRPC1,TRP cation channel subfamily M member 2,and TRP cation channel subfamily M member 6)to be significantly associated with HCC patient prognosis(P<0.05).These genes were utilized to establish a TRP-related risk model.Patients were separated into low-and high-risk groups based on the expression of these genes,and high-risk patients exhibited a significantly poorer prognosis(P=0.001).Functional analyses highlighted pronounced differences in the immune status of patients in these two groups and associated enriched immune pathways.TRPC1 was identified as a candidate gene in this family worthy of further study,with HCC patients expressing higher TRPC1 levels exhibiting poorer survival outcomes.Consistently,quantitative,immunohistochemistry,and western blot analyses revealed increased TRPC1 expression in HCC.CONCLUSION These three TRP genes help determine HCC patient prognosis,providing insight into tumor immune status and immunological composition.These findings will help design combination therapies including immunotherapeutic and anti-TRP agents.
基金MEXT,KAKENHI,No.15K08978,No.22790677 and No.25860571a MEXT-Supported Program supporting research activities of female researchers+1 种基金the Clinical Research Foundationthe Central Research Institute of Fukuoka University,No.151045 and No.147104
文摘AIM To investigate the anti-fibrotic effects of the traditional oriental herbal medicine Daikenchuto(DKT) associated with transient receptor potential ankyrin 1(TRPA1) channels in intestinal myofibroblasts. METHODS Inflammatory and fibrotic changes were detected in a2,4,6-trinitrobenzenesulfonic acid(TNBS) chronic colitis model of wild-type and TRPA1-knockout(TRPA1-KO) mice via pathological staining and immunoblotting analysis.Ca^(2+) imaging experiments examined the effects of DKT and its components/ingredients on intestinal myofibroblast(In Myo Fib) cell TRPA1 channel function.Profibrotic factors and transforming growth factor (TGF) -β1-associated signaling were tested in an In Myo Fib cell line by q PCR and immunoblotting experiments.Samples from non-stenotic and stenotic regions of the intestines of patients with Crohn’s disease (CD) were used for pathological analysis. RESULTS Chronic treatment with TNBS caused more severe inflammation and fibrotic changes in TRPA1-KO than in wild-type mice.A one-week enema administration of DKT reduced fibrotic lesions in wild-type but not in TRPA1-KO mice.The active ingredients of DKT,i.e.,hydroxyα-sanshool and 6-shogaol,induced Ca^(2+) influxes in In Myo Fib,and this was antagonized by co-treatment with a selective TRPA1 channel blocker,HC-030031.DKT counteracted TGF-β1-induced expression of TypeⅠcollagen andα-smooth muscle actin (α-SMA) ,which were accompanied by a reduction in the phosphorylation of Smad-2 and p38-mitogen-activated protein kinase (p38-MAPK) and the expression of myocardin.Importantly,24-h incubation with a DKT active component Japanese Pepper increased the m RNA and protein expression levels of TRPA1 in In Myo Fibs,which in turn negatively regulated collagen synthesis.In the stenotic regions of the intestines of CD patients,TRPA1 expression was significantly enhanced.CONCLUSION The effects of DKT on the expression and activation of the TRPA1 channel could be advantageous for suppressing intestinal fibrosis,and benefit inflammatory bowel disease treatment.
基金supported by the Research Basis Formation Supporting Project for Private University
文摘Transient receptor potential channel A1 is one of the important transducers of noxious stimuli in the primary afferents, which may contribute to generation of neurogenic inflammation and hyperalgesia. The present study was designed to investigate if activation of transient receptor potential channel A1 may induce calcitonin gene-related peptide release from the primary afferent neurons. We found that application of allyl isothiocyanate, a transient receptor potential channel A1 activator, caused calcitonin gene-related peptide release from the cultured rat dorsal root ganglion neurons. Knock- down of transient receptor potential channel A1 with an antisense oligodeoxynucleotide prevented calcitonin gene-related peptide release by allyl isothiocyanate application in cultured dorsal root ganglion neurons. Thus, we concluded that transient receptor potential channel A1 activation caused calcitonin gene-related peptide release in sensory neurons.
基金supported by the National Natural Science Foundation of China,No.81171178the Natural Science Foundation of Shanxi Province in China,No.2012011036-3Scientific Research Foundation of Shanxi Province of China for the Returned Overseas Chinese Scholars,No.2013011054-2
文摘The transient receptor potential cation channel subfamily V member 1（TRPV1） provides the sensation of pain（nociception）. However, it remains unknown whether TRPV1 is activated after peripheral nerve injury, or whether activation of TRPV1 affects neural regeneration. In the present study, we established rat models of unilateral sciatic nerve crush injury, with or without pretreatment with AMG517（300 mg/kg）, a TRPV1 antagonist, injected subcutaneously into the ipsilateral paw 60 minutes before injury. At 1 and 2 weeks after injury, we performed immunofluorescence staining of the sciatic nerve at the center of injury, at 0.3 cm proximal and distal to the injury site, and in the dorsal root ganglia. Our results showed that Wallerian degeneration occurred distal to the injury site, and neurite outgrowth and Schwann cell regeneration occurred proximal to the injury. The number of regenerating myelinated and unmyelinated nerve clusters was greater in the AMG517-pretreated rats than in the vehicle-treated group, most notably 2 weeks after injury. TRPV1 expression in the injured sciatic nerve and ipsilateral dorsal root ganglia was markedly greater than on the contralateral side. Pretreatment with AMG517 blocked this effect. These data indicate that TRPV1 is activated or overexpressed after sciatic nerve crush injury, and that blockade of TRPV1 may accelerate regeneration of the injured sciatic nerve.
文摘BACKGROUND Transient receptor potential vanilloid-1(TRPV1),a nonselective cation channel,is activated by capsaicin,a pungent ingredient of hot pepper.Previous studies have suggested a link between obesity and capsaicin-associated pathways,and activation of TRPV1 may provide an alternative approach for obesity treatment.However,data on the TRPV1 distribution in human gastric mucosa are limited,and the degree of TRPV1 distribution in the gastric and duodenal mucosal cells of obese people in comparison with normal-weight individuals is unknown.AIM To clarify gastric and duodenal mucosal expression of TRPV1 in humans and compare TRPV1 expression in obese and healthy individuals.METHODS Forty-six patients with a body mass index(BMI)of>40 kg/m^(2) and 20 patients with a BMI between 18-25 kg/m^(2) were included.Simultaneous biopsies from the fundus,antrum,and duodenum tissues were obtained from subjects between the ages of 18 and 65 who underwent esophagogastroduodenoscopy.Age,sex,history of alcohol and cigarette consumption,and past medical history regarding chronic diseases and medications were accessed from patient charts and were analyzed accordingly.Evaluation with anti-TRPV1 antibody was performed separately according to cell types in the fundus,antrum,and duodenum tissues using an immunoreactivity score.Data were analyzed using SPSS 17.0.RESULTS TRPV1 expression was higher in the stomach than in the duodenum and was predominantly found in parietal and chief cells of the fundus and mucous and foveolar cells of the antrum.Unlike foveolar cells in the antrum,TRPV1 was relatively low in foveolar cells in the fundus(4.92±0.49 vs 0.48±0.16,P<0.01,Mann-Whitney U test).Additionally,the mucous cells in the duodenum also had low levels of TRPV1 compared to mucous cells in the antrum(1.33±0.31 vs 2.95±0.46,P<0.01,Mann-Whitney U test).TRPV1 expression levels of different cell types in the fundus,antrum,and duodenum tissues of the morbidly obese group were similar to those of the control group.Staining with TRPV1 in fundus chief cells and antrum and duodenum mucous cells was higher in patients aged≥45 years than in patients<45 years(3.03±0.42,4.37±0.76,2.28±0.55 vs 1.9±0.46,1.58±0.44,0.37±0.18,P=0.03,P<0.01,P<0.01,respectively,Mann-Whitney U test).The mean staining levels of TRPV1 in duodenal mucous cells in patients with diabetes and hypertension were higher than those in patients without diabetes and hypertension(diabetes:2.11±0.67 vs 1.02±0.34,P=0.04;hypertension:2.42±0.75 vs 1.02±0.33,P<0.01 Mann-Whitney U test).CONCLUSION The expression of TRPV1 is unchanged in the gastroduodenal mucosa of morbidly obese patients demonstrating that drugs targeting TRPV1 may be effective in these patients.
文摘Background: Transient receptor potential ankyrin (TRPA) 1 is known as a peripheral initiator of acute inflammation and hyperalgesia. However, its role in the facilitation of innate immune responses followed by resolution of the inflammation triggered by a surgical incision has not been fully investigated. Therefore, we evaluated the mechanism by which TRPA1 regulates the inflammatory responses mainly facilitated by neutrophils and macrophages in the early course of wound repair after an incision. Methods: Plantar incision was performed in wild-type and TRPA1-/- mice. The infiltration of polymorphonuclear neutrophils, macrophage phenotype, and induction of inflammatory mediators were assessed for 7 days postoperatively. Results: TRPA1-/-?mice exhibited decreased infiltration of polymorphonuclear neutrophilscompared with wild-type mice on day 1. Consistently, the influx of F4/80+ iNOS+ proinflammatory M1 macrophages to incised sites was markedly decreased on day 2. Similarly, F4/80+ CD206+M2 macrophages, which regulate the resolution of inflammation and promote wound healing in the later phase of acute inflammation, were significantly decreased in TRPA1-/- compared with those in wild-type mice on day 7. In addition, the induction of heme oxygenase-1, which promotes wound healing by switching phenotype of macrophages, was decreased in the early phase of acute inflammation, whereas the expression of proinflammatory mediators such as tumor necrosis factor and cyclooxygenase-2, and 15-lipoxygenase, which are involved in the resolution of inflammation was increased in the late phase in TRPA1-/- mice. Conclusions: Early innate immune responses including neutrophil infiltration and macrophage polarization at incised sites were inhibited in TRPA1-/- mice, associated with increased pro-inflammatory mediators in later phase. Peripheral TRPA1 may facilitate the acute inflammatory process, leading to the promotion of macrophage-mediated resolution of inflammation and wound repair after a surgical incision.
文摘Background: It is important to maintain skin homeostasis for cosmetic and medical reasons. Many ceramide-related ingredients and cosmetics have been developed to improve the skin barrier function and skin hydration. Similar to extracellular lipids, the cornified envelope, which is a structure formed beneath the plasma membrane, contributes to the skin barrier function as a scaffold for extracellular lipids. Therefore, in this study, we focused on transglutaminase 1 (TGM1) which is the key enzyme for formation of the cornified envelope Objective: The objectives of this study were to identify compounds that could upregulate the expression of TGM1 and evaluate their underlying action mechanisms. Methods: Expression of the transient receptor potential channel vanilloid subfamily member 4 (TRPV4) at the mRNA and protein levels was estimated by PCR and western blotting. Effects of baicalein and Salvia officinalis (SO) extract on TGM1 mRNA expression were measured by PCR. The involvement of TRPV4 in TGM1 mRNA expression was evaluated by the inhibition and silencing of TRPV4. Results: TRPV4 was expressed in both basal cell-like HaCaT cells and suprabasal cell-like HaCaT cells. Baicalein and SO extract upregulated TGM1 mRNA expression in basal cell-like HaCaT cells. However, inhibition and silencing of TRPV4 abrogated the effects of baicalein and SO extract. Conclusion: Baicalein and SO extract upregulated the expression of TGM1 mRNA via the activation of TRPV4, suggesting that it may improve the skin barrier function by enhancing cornified envelope formation.
