Background:Cisplatin is a chemotherapeutic agent commonly used clinically for the treatment of various human cancers.Patients often reduce the use of cisplatin due to its side effects,which in turn affects its treatme...Background:Cisplatin is a chemotherapeutic agent commonly used clinically for the treatment of various human cancers.Patients often reduce the use of cisplatin due to its side effects,which in turn affects its treatment.This study explored the mechanism of action of safflower extract as an adjuvant traditional Chinese medicine for chemotherapy.Methods:Primary human follicle dermal papilla cells(HFDPCs)were used as target cells for cisplatininduced damage to hair cells.Western blotting was used to investigate the molecular targets of cisplatin and safflower extract in causing HFDPCs damage.Cell survival and cell cycle were analyzed by mitochondrial staining reagent WST-1 and propidium iodide.Results:Cisplatin could reduce the viability of HFDPCs without causing cell death.Cisplatin increased the level of phospho-Rad17 in HFDPCs and activated the Chk1/Cdc25C signaling to reduce the expression of Cdc2 protein,thereby arresting the cells in the G2/M phase.The combination of safflower extract and the flavonoids could effectively inhibit the signal transduction of Rad17/Chk1/Cdc25 in cisplatin-treated cells and reduce the cell population in the G2/M phase.Finally,we also confirmed that safflower extract could effectively inhibit the damage to HFDPCs caused by cisplatin,mainly at the level of reducing the DNA damage caused by cisplatin.Conclusions:Safflower extract can be used as an adjuvant Chinese medicine for chemotherapy to reduce the damage caused by chemotherapy to normal hair follicle cells.展开更多
Objective: To screen and clone differentially expressed genes of dermal papillae cells (DPC) with aggregative behavior, and to explore the molecular mechanism of their aggregation. Methods: Total RNAs were extracted f...Objective: To screen and clone differentially expressed genes of dermal papillae cells (DPC) with aggregative behavior, and to explore the molecular mechanism of their aggregation. Methods: Total RNAs were extracted from DPC with and without aggregative behavior and double strand cDNAs were synthesized by using SMART cDNA synthesis, respectively. The cDNA fragments of differentially expressed genes in DPCs with aggregative behavior were isolated by suppression subtractive hybridization. Positive clones were screened by PCR method and verified by cDNA dot blot, Northern blot and then analyzed through homologous retrieving. Results: A subtractive cDNA library of DPC with aggregative behavior has been successfully constructed. The result of screening and cloning of the library showed that, DPC with aggregative behavior could expresse genes related to homologous aggregation, proliferation and cycle control, including known genes (capping protein, paladin, vascular endothelial growth factor), hematopoietic stem/progenitor cells (HSPC) related clone (HSPC011 and HSPC016) and a new gene. Conclusion: The construction of subtracted library of DPC lays solid foundation for screening and cloning new and specific genes related to aggregative behavior of DPC. Several genes might be cooperatively involved in the homologous aggregation, proliferation and cycle control of DPC. Among these genes, capping protein and palladin might be closely related to the aggregative behavior of dermal papilla cells, and VEGF and HSPC related clone would be responsible for the status of higher proliferation of dermal papilla cells.展开更多
Objective： To clone the full-length cDNA sequence of HSPC016 gene, an aggregative growth related gene in dermal papilla cells （DPC）, and analyze its characteristics and predict its biological function. Methods： Ra...Objective： To clone the full-length cDNA sequence of HSPC016 gene, an aggregative growth related gene in dermal papilla cells （DPC）, and analyze its characteristics and predict its biological function. Methods： Rapid amplification of cDNA ends （RACE） technology was entailed to amplify the 5＇ and 3＇ sequences of HSPC016. The amplified fragments were TA-cloned, sequenced and spliced together to obtain the full-length cDNA. Its chromosome localization, domain and possible function were analyzed by bioinformatic methods. Results.. Two isoforms, 400 bp and 493 bp, were obtained. The gene was mapped on chromosome 3q21. 31, and was conservative on evolution. HSPC016, a 64aa protein, belongs to PD053992 protein family and its functional domain was homologous to T2FA gene. Conclusion： PISPC016 may be related to transcriptional regulation and its protein product may act as a subunit of a transcriptional complex and play a role on DPC growth and differentiation through facilitating or suppressing other genes＇ transcription within the nucleus.展开更多
The reconstitution of a fully organized and functional hair follicle from dissociated cells propagated under defined tissue culture conditions is a challenge stillpending in tissue engineering. The loss of hair follic...The reconstitution of a fully organized and functional hair follicle from dissociated cells propagated under defined tissue culture conditions is a challenge stillpending in tissue engineering. The loss of hair follicles caused by injuries or pathologies such as alopecia not only affects the patients' psychological well-being, but also endangers certain inherent functions of the skin. It is then of great interest to find different strategies aiming to regenerate or neogenerate the hair follicle under conditions proper of an adult individual. Based upon current knowledge on the epithelial and dermal cells and their interactions during the embryonic hair generation and adult hair cycling, many researchers have tried to obtain mature hair follicles using different strategies and approaches depending on the causes of hair loss. This review summarizes current advances in the different experimental strategies to regenerate or neogenerate hair follicles, with emphasis on those involving neogenesis of hair follicles in adult individuals using isolated cells and tissue engineering. Most of these experiments were performed using rodent cells, particularly from embryonic or newborn origin. However, no successful strategy to generate human hair follicles from adult cells has yet been reported. This review identifies several issues that should be considered to achieve this objective. Perhaps the most important challenge is to provide threedimensional culture conditions mimicking the structure of living tissue. Improving culture conditions that allow the expansion of specific cells while protecting their inductive properties, as well as methods for selecting populations of epithelial stem cells, should give us the necessary tools to overcome the difficulties that constrain human hair follicle neogenesis. An analysis of patent trends shows that the number of patent applications aimed at hair follicle regeneration and neogenesis has been increasing during the last decade. This field is attractive not only to academic researchers but also to the companies that own almost half of the patents in this field.展开更多
BACKGROUND Dermal papillae(DP)and outer root sheath(ORS)cells play important roles in hair growth and regeneration by regulating the activity of hair follicle(HF)cells.AIM To investigate the effects of human mesenchym...BACKGROUND Dermal papillae(DP)and outer root sheath(ORS)cells play important roles in hair growth and regeneration by regulating the activity of hair follicle(HF)cells.AIM To investigate the effects of human mesenchymal stem cell-derived extracellular vesicles(hMSC-EVs)on DP and ORS cells as well as HFs.EVs are known to regulate various cellular functions.However,the effects of hMSC-EVs on hair growth,particularly on human-derived HF cells(DP and ORS cells),and the possible mechanisms underlying these effects are unknown.METHODS hMSC-EVs were isolated and characterized using transmission electron microscopy,nanoparticle tracking analysis,western blotting,and flow cytometry.The activation of DP and ORS cells was analyzed using cellular proliferation,migration,western blotting,and real-time polymerase chain reaction.HF growth was evaluated ex vivo using human HFs.RESULTS Wnt3a is present in a class of hMSC-EVs and associated with the EV membrane.hMSC-EVs promote the proliferation of DP and ORS cells.Moreover,they translocateβ-catenin into the nucleus of DP cells by increasing the expression ofβ-catenin target transcription factors(Axin2,EP2 and LEF1)in DP cells.Treatment with hMSC-EVs also promoted the migration of ORS cells and enhanced the expression of keratin(K)differentiation markers(K6,K16,K17,and K75)in ORS cells.Furthermore,treatment with hMSC-EVs increases hair shaft elongation in cultured human HFs.CONCLUSION These findings suggest that hMSC-EVs are potential candidates for further preclinical and clinical studies on hair loss treatment.展开更多
Background:Non-healing wounds are an intractable problem of major clinical relevance.Evidence has shown that dermal papilla cells(DPCs)may regulate the wound-healing process by secreting extracellular vesicles(EVs).Ho...Background:Non-healing wounds are an intractable problem of major clinical relevance.Evidence has shown that dermal papilla cells(DPCs)may regulate the wound-healing process by secreting extracellular vesicles(EVs).However,low isolation efficiency and restricted cell viability hinder the applications of DPC-EVs in wound healing.In this study,we aimed to develop novel 3D-DPC spheroids(tdDPCs)based on self-feeder 3D culture and to evaluate the roles of tdDPC-EVs in stimulating angiogenesis and skin wound healing.Methods:To address the current limitations of DPC-EVs,we previously developed a self-feeder 3D culture method to construct tdDPCs.DPCs and tdDPCs were identified using immunofluorescence staining and flow cytometry.Subsequently,we extracted EVs from the cells and compared the effects of DPC-EVs and tdDPC-EVs on human umbilical vein endothelial cells(HUVECs)in vitro using immunofluorescence staining,a scratch-wound assay and a Transwell assay.We simultaneously established a murine model of full-thickness skin injury and evaluated the effects of DPC-EVs and tdDPC-EVs on wound-healing efficiency in vivo using laser Doppler,as well as hematoxylin and eosin,Masson,CD31 andα-SMA staining.To elucidate the underlying mechanism,we conducted RNA sequencing(RNA-seq)of tdDPC-EV-and phosphate-buffered saline-treated HUVECs.To validate the RNA-seq data,we constructed knockdown and overexpression vectors of Krüppel-like factor 4(KLF4).Western blotting,a scratch-wound assay,a Transwell assay and a tubule-formation test were performed to detect the protein expression,cell migration and lumen-formation ability of KLF4 and vascular endothelial growth factor A(VEGFA)in HUVECs incubated with tdDPC-EVs after KLF4 knockdown or overexpression.Dual-luciferase reporter gene assays were conducted to verify the activation effect of KLF4 on VEGFA.Results:We successfully cultured tdDPCs and extracted EVs from DPCs and tdDPCs.The tdDPC-EVs significantly promoted the proliferation,lumen formation and migration of HUVECs.Unlike DPC-EVs,tdDPC-EVs exhibited significant advantages in terms of promoting angiogenesis,accelerating wound healing and enhancing wound-healing efficiency both in vitro and in vivo.Bioinformatics analysis and further functional experiments verified that the tdDPC-EV-regulated KLF4/VEGFA axis is pivotal in accelerating wound healing.Conclusions:3D cultivation can be utilized as an innovative optimization strategy to effectively develop DPC-derived EVs for the treatment of skin wounds.tdDPC-EVs significantly enhance wound healing via KLF4/VEGFA-driven angiogenesis.展开更多
The dermal papilla cells in hair follicles function as critical regulators of hair growth.In particular,alopecia areata(AA)is closely related to the malfunctioning of the human dermal papilla cells(hDPCs).Thus,identif...The dermal papilla cells in hair follicles function as critical regulators of hair growth.In particular,alopecia areata(AA)is closely related to the malfunctioning of the human dermal papilla cells(hDPCs).Thus,identifying the regulatory mechanism of hDPCs is important in inducing hair follicle(HF)regeneration in AA patients.Recently,growing evidence has indicated that 3 untranslated regions(3 UTR)of key genes may participate in the regulatory circuitry underlying cell differentiation and diseases through a socalled competing endogenous mechanism,but none have been reported in HF regeneration.Here,we demonstrate that the 3 UTR of junctional adhesion molecule A(JAM-A)could act as an essential competing endogenous RNA to maintain hDPCs function and promote HF regeneration in AA.We showed that the 3 UTR of JAM-A shares many microRNA(miRNA)response elements,especially miR-221–3p,with versican(VCAN)mRNA,and JAM-A 3 UTR could directly modulate the miRNA-mediated suppression of VCAN in self-renewing hDPCs.Furthermore,upregulated VCAN can in turn promote the expression level of JAM-A.Overall,we propose that JAM-A 3 UTR forms a feedback loop with VCAN and miR-221–3p to regulate hDPC maintenance,proliferation,and differentiation,which may lead to developing new therapies for hair loss.展开更多
Banana flowers contain various bioactive components, including several antioxidants with anti-inflammatory effects. However, it is unclear whether they can reduce and prevent hair loss. This study examines the effect ...Banana flowers contain various bioactive components, including several antioxidants with anti-inflammatory effects. However, it is unclear whether they can reduce and prevent hair loss. This study examines the effect of banana flower extracts on preventing hair loss and strengthening hair roots. The banana flower extract(HappyAngel^(■))was used to treat human hair follicle dermal papilla cells(HFDPCs)and the expression of reactive oxygen species(ROS), dihydrotestosterone(DHT), and hair-related genes(SRD5A1, SRD5A2, AR, and KROX20)were monitored. Fifty subjects were divided into a placebo group and a banana flower group. The experimental group consumed banana flower extract daily for twelve weeks and then underwent hair testing, hair-related genes analysis, collection of hair loss, and questionnaires. The results showed that the banana flower extract significantly increased hair cell growth and decreased the expression of ROS, DHT, and hair follicle growth inhibition-related SRD5A1, SRD5A2, and AR genes, and significantly increased the expression of hair growth-related KROX20 gene in HFDPCs. Consuming banana flower extract for twelve weeks increased the hair root diameter and reduced hair loss and scalp redness compared to the placebo group. Thus, banana flower extract(HappyAngel^(■))can stimulate hair growth and inhibit the activation of hair loss genes.展开更多
基金supported by the Taipei Tzu Chi Hospital through grants from the Buddhist Tzu Chi Medical Foundation under the Numbers TCRD-TPE-110-13 and TCRD-TPE-111-23,Taipei,Taiwan.
文摘Background:Cisplatin is a chemotherapeutic agent commonly used clinically for the treatment of various human cancers.Patients often reduce the use of cisplatin due to its side effects,which in turn affects its treatment.This study explored the mechanism of action of safflower extract as an adjuvant traditional Chinese medicine for chemotherapy.Methods:Primary human follicle dermal papilla cells(HFDPCs)were used as target cells for cisplatininduced damage to hair cells.Western blotting was used to investigate the molecular targets of cisplatin and safflower extract in causing HFDPCs damage.Cell survival and cell cycle were analyzed by mitochondrial staining reagent WST-1 and propidium iodide.Results:Cisplatin could reduce the viability of HFDPCs without causing cell death.Cisplatin increased the level of phospho-Rad17 in HFDPCs and activated the Chk1/Cdc25C signaling to reduce the expression of Cdc2 protein,thereby arresting the cells in the G2/M phase.The combination of safflower extract and the flavonoids could effectively inhibit the signal transduction of Rad17/Chk1/Cdc25 in cisplatin-treated cells and reduce the cell population in the G2/M phase.Finally,we also confirmed that safflower extract could effectively inhibit the damage to HFDPCs caused by cisplatin,mainly at the level of reducing the DNA damage caused by cisplatin.Conclusions:Safflower extract can be used as an adjuvant Chinese medicine for chemotherapy to reduce the damage caused by chemotherapy to normal hair follicle cells.
文摘Objective: To screen and clone differentially expressed genes of dermal papillae cells (DPC) with aggregative behavior, and to explore the molecular mechanism of their aggregation. Methods: Total RNAs were extracted from DPC with and without aggregative behavior and double strand cDNAs were synthesized by using SMART cDNA synthesis, respectively. The cDNA fragments of differentially expressed genes in DPCs with aggregative behavior were isolated by suppression subtractive hybridization. Positive clones were screened by PCR method and verified by cDNA dot blot, Northern blot and then analyzed through homologous retrieving. Results: A subtractive cDNA library of DPC with aggregative behavior has been successfully constructed. The result of screening and cloning of the library showed that, DPC with aggregative behavior could expresse genes related to homologous aggregation, proliferation and cycle control, including known genes (capping protein, paladin, vascular endothelial growth factor), hematopoietic stem/progenitor cells (HSPC) related clone (HSPC011 and HSPC016) and a new gene. Conclusion: The construction of subtracted library of DPC lays solid foundation for screening and cloning new and specific genes related to aggregative behavior of DPC. Several genes might be cooperatively involved in the homologous aggregation, proliferation and cycle control of DPC. Among these genes, capping protein and palladin might be closely related to the aggregative behavior of dermal papilla cells, and VEGF and HSPC related clone would be responsible for the status of higher proliferation of dermal papilla cells.
基金Supported by the National Natural Science Foundation of China (No.30200249)
文摘Objective： To clone the full-length cDNA sequence of HSPC016 gene, an aggregative growth related gene in dermal papilla cells （DPC）, and analyze its characteristics and predict its biological function. Methods： Rapid amplification of cDNA ends （RACE） technology was entailed to amplify the 5＇ and 3＇ sequences of HSPC016. The amplified fragments were TA-cloned, sequenced and spliced together to obtain the full-length cDNA. Its chromosome localization, domain and possible function were analyzed by bioinformatic methods. Results.. Two isoforms, 400 bp and 493 bp, were obtained. The gene was mapped on chromosome 3q21. 31, and was conservative on evolution. HSPC016, a 64aa protein, belongs to PD053992 protein family and its functional domain was homologous to T2FA gene. Conclusion： PISPC016 may be related to transcriptional regulation and its protein product may act as a subunit of a transcriptional complex and play a role on DPC growth and differentiation through facilitating or suppressing other genes＇ transcription within the nucleus.
基金Supported by the Agencia Nacional de Producción Científica y Tecnológica(ANPCyT),No.ANR BIO 0032/10
文摘The reconstitution of a fully organized and functional hair follicle from dissociated cells propagated under defined tissue culture conditions is a challenge stillpending in tissue engineering. The loss of hair follicles caused by injuries or pathologies such as alopecia not only affects the patients' psychological well-being, but also endangers certain inherent functions of the skin. It is then of great interest to find different strategies aiming to regenerate or neogenerate the hair follicle under conditions proper of an adult individual. Based upon current knowledge on the epithelial and dermal cells and their interactions during the embryonic hair generation and adult hair cycling, many researchers have tried to obtain mature hair follicles using different strategies and approaches depending on the causes of hair loss. This review summarizes current advances in the different experimental strategies to regenerate or neogenerate hair follicles, with emphasis on those involving neogenesis of hair follicles in adult individuals using isolated cells and tissue engineering. Most of these experiments were performed using rodent cells, particularly from embryonic or newborn origin. However, no successful strategy to generate human hair follicles from adult cells has yet been reported. This review identifies several issues that should be considered to achieve this objective. Perhaps the most important challenge is to provide threedimensional culture conditions mimicking the structure of living tissue. Improving culture conditions that allow the expansion of specific cells while protecting their inductive properties, as well as methods for selecting populations of epithelial stem cells, should give us the necessary tools to overcome the difficulties that constrain human hair follicle neogenesis. An analysis of patent trends shows that the number of patent applications aimed at hair follicle regeneration and neogenesis has been increasing during the last decade. This field is attractive not only to academic researchers but also to the companies that own almost half of the patents in this field.
基金Supported by Basic Science Research Program through the National Research Foundation of Korea (NRF), Funded by the Ministry of Education, No. NRF-2019R1I1A1A01061296 and No. NRF-2021R1I1A1A01040732Korea Health Technology R & D Project through the Korea Health Industry Development Institute, Funded By the Ministry of Health & Welfare, Republic of Korea, No. HI15C0001
文摘BACKGROUND Dermal papillae(DP)and outer root sheath(ORS)cells play important roles in hair growth and regeneration by regulating the activity of hair follicle(HF)cells.AIM To investigate the effects of human mesenchymal stem cell-derived extracellular vesicles(hMSC-EVs)on DP and ORS cells as well as HFs.EVs are known to regulate various cellular functions.However,the effects of hMSC-EVs on hair growth,particularly on human-derived HF cells(DP and ORS cells),and the possible mechanisms underlying these effects are unknown.METHODS hMSC-EVs were isolated and characterized using transmission electron microscopy,nanoparticle tracking analysis,western blotting,and flow cytometry.The activation of DP and ORS cells was analyzed using cellular proliferation,migration,western blotting,and real-time polymerase chain reaction.HF growth was evaluated ex vivo using human HFs.RESULTS Wnt3a is present in a class of hMSC-EVs and associated with the EV membrane.hMSC-EVs promote the proliferation of DP and ORS cells.Moreover,they translocateβ-catenin into the nucleus of DP cells by increasing the expression ofβ-catenin target transcription factors(Axin2,EP2 and LEF1)in DP cells.Treatment with hMSC-EVs also promoted the migration of ORS cells and enhanced the expression of keratin(K)differentiation markers(K6,K16,K17,and K75)in ORS cells.Furthermore,treatment with hMSC-EVs increases hair shaft elongation in cultured human HFs.CONCLUSION These findings suggest that hMSC-EVs are potential candidates for further preclinical and clinical studies on hair loss treatment.
基金supported by the National Natural Science Foundation of China(No.82272268)the Industry-University-Research Innovation Fund of China(2021JH030).
文摘Background:Non-healing wounds are an intractable problem of major clinical relevance.Evidence has shown that dermal papilla cells(DPCs)may regulate the wound-healing process by secreting extracellular vesicles(EVs).However,low isolation efficiency and restricted cell viability hinder the applications of DPC-EVs in wound healing.In this study,we aimed to develop novel 3D-DPC spheroids(tdDPCs)based on self-feeder 3D culture and to evaluate the roles of tdDPC-EVs in stimulating angiogenesis and skin wound healing.Methods:To address the current limitations of DPC-EVs,we previously developed a self-feeder 3D culture method to construct tdDPCs.DPCs and tdDPCs were identified using immunofluorescence staining and flow cytometry.Subsequently,we extracted EVs from the cells and compared the effects of DPC-EVs and tdDPC-EVs on human umbilical vein endothelial cells(HUVECs)in vitro using immunofluorescence staining,a scratch-wound assay and a Transwell assay.We simultaneously established a murine model of full-thickness skin injury and evaluated the effects of DPC-EVs and tdDPC-EVs on wound-healing efficiency in vivo using laser Doppler,as well as hematoxylin and eosin,Masson,CD31 andα-SMA staining.To elucidate the underlying mechanism,we conducted RNA sequencing(RNA-seq)of tdDPC-EV-and phosphate-buffered saline-treated HUVECs.To validate the RNA-seq data,we constructed knockdown and overexpression vectors of Krüppel-like factor 4(KLF4).Western blotting,a scratch-wound assay,a Transwell assay and a tubule-formation test were performed to detect the protein expression,cell migration and lumen-formation ability of KLF4 and vascular endothelial growth factor A(VEGFA)in HUVECs incubated with tdDPC-EVs after KLF4 knockdown or overexpression.Dual-luciferase reporter gene assays were conducted to verify the activation effect of KLF4 on VEGFA.Results:We successfully cultured tdDPCs and extracted EVs from DPCs and tdDPCs.The tdDPC-EVs significantly promoted the proliferation,lumen formation and migration of HUVECs.Unlike DPC-EVs,tdDPC-EVs exhibited significant advantages in terms of promoting angiogenesis,accelerating wound healing and enhancing wound-healing efficiency both in vitro and in vivo.Bioinformatics analysis and further functional experiments verified that the tdDPC-EV-regulated KLF4/VEGFA axis is pivotal in accelerating wound healing.Conclusions:3D cultivation can be utilized as an innovative optimization strategy to effectively develop DPC-derived EVs for the treatment of skin wounds.tdDPC-EVs significantly enhance wound healing via KLF4/VEGFA-driven angiogenesis.
文摘目的探索DNA损伤诱导转录因子4(DNA damage induced transcription factor 4,DDIT4)在毛乳头细胞氧化应激损伤中的保护作用及其机制。方法使用长波紫外线(ultraviolet radiation A,UVA)和过氧化氢(H 2 O 2)建立毛乳头细胞氧化应激模型;CCK-8检测不同处理条件下的细胞活力,利用2′,7′-二氯荧光素二乙酸酯(2′,7′-dichlorofluorescein diacetate,DCFH-DA)试剂检测细胞内活性氧(ROS)的变化;电镜观察自噬小体;Western blot观察DDIT4及自噬相关指标微管相关蛋白1轻链3(microtubule-associated protein 1 light chain 3,LC3)、泛素结合蛋白(ubiquitin-binding protein P62,P62)、雷帕霉素哺乳动物靶蛋白(mammalian target of rapamycin,mTOR)、p-mTOR的表达情况。结果UVA和H 2 O 2导致毛乳头细胞内ROS升高,活力下降(P<0.05);氧化应激环境下毛乳头细胞内的DDIT4表达增加(P<0.05),而抗氧化剂N-乙酰基-L-半胱氨酸(N-acetyl-L-cysteine,NAC)可有效抑制此效应(P<0.05);UVA或H 2 O 2处理后毛乳头细胞内自噬水平升高,表现为自噬体数量增多,LC3Ⅱ/Ⅰ比值增高(P<0.05),P62表达下降(P<0.05),3-甲基腺嘌呤(3-methyladenine,3-MA)阻断自噬可观察到细胞活力进一步降低(P<0.05),细胞内ROS增多(P<0.05),反之,雷帕霉素(rapamycin,RAPA)可增加自噬水平提升氧化条件下毛乳头细胞活力,减少细胞内ROS生成(P<0.05);下调DDIT4表达可使氧化应激环境下毛乳头细胞自噬减弱,LC3Ⅱ/Ⅰ减少(P<0.05),p-mTOR/mTOR、P62增加(P<0.05),细胞活力下降(P<0.05),细胞内ROS增多(P<0.05)。结论DDIT4可能通过自噬缓解毛乳头细胞氧化应激损伤。
基金supported by the National Natural Science Foundation of China(Grants No.81772075,81772076,and 32071186).
文摘The dermal papilla cells in hair follicles function as critical regulators of hair growth.In particular,alopecia areata(AA)is closely related to the malfunctioning of the human dermal papilla cells(hDPCs).Thus,identifying the regulatory mechanism of hDPCs is important in inducing hair follicle(HF)regeneration in AA patients.Recently,growing evidence has indicated that 3 untranslated regions(3 UTR)of key genes may participate in the regulatory circuitry underlying cell differentiation and diseases through a socalled competing endogenous mechanism,but none have been reported in HF regeneration.Here,we demonstrate that the 3 UTR of junctional adhesion molecule A(JAM-A)could act as an essential competing endogenous RNA to maintain hDPCs function and promote HF regeneration in AA.We showed that the 3 UTR of JAM-A shares many microRNA(miRNA)response elements,especially miR-221–3p,with versican(VCAN)mRNA,and JAM-A 3 UTR could directly modulate the miRNA-mediated suppression of VCAN in self-renewing hDPCs.Furthermore,upregulated VCAN can in turn promote the expression level of JAM-A.Overall,we propose that JAM-A 3 UTR forms a feedback loop with VCAN and miR-221–3p to regulate hDPC maintenance,proliferation,and differentiation,which may lead to developing new therapies for hair loss.
文摘Banana flowers contain various bioactive components, including several antioxidants with anti-inflammatory effects. However, it is unclear whether they can reduce and prevent hair loss. This study examines the effect of banana flower extracts on preventing hair loss and strengthening hair roots. The banana flower extract(HappyAngel^(■))was used to treat human hair follicle dermal papilla cells(HFDPCs)and the expression of reactive oxygen species(ROS), dihydrotestosterone(DHT), and hair-related genes(SRD5A1, SRD5A2, AR, and KROX20)were monitored. Fifty subjects were divided into a placebo group and a banana flower group. The experimental group consumed banana flower extract daily for twelve weeks and then underwent hair testing, hair-related genes analysis, collection of hair loss, and questionnaires. The results showed that the banana flower extract significantly increased hair cell growth and decreased the expression of ROS, DHT, and hair follicle growth inhibition-related SRD5A1, SRD5A2, and AR genes, and significantly increased the expression of hair growth-related KROX20 gene in HFDPCs. Consuming banana flower extract for twelve weeks increased the hair root diameter and reduced hair loss and scalp redness compared to the placebo group. Thus, banana flower extract(HappyAngel^(■))can stimulate hair growth and inhibit the activation of hair loss genes.
