Cheng Xiu, Huining Zheng, Manfei Jiang, Jiaxu Li, Yanhong Zhou, Lan Mu, Weisong Liu
{"title":"mscs来源的表达mir -150-5p的外泌体通过PTEN激活PI3K/AKT通路促进皮肤伤口愈合。","authors":"Cheng Xiu, Huining Zheng, Manfei Jiang, Jiaxu Li, Yanhong Zhou, Lan Mu, Weisong Liu","doi":"10.15283/ijsc21135","DOIUrl":null,"url":null,"abstract":"<p><strong>Background and objectives: </strong>The goal of this study was to investigate the mechanism of mesenchymal stem cell (MSC)-derived microRNA (miR)-150-5p-expressing exosomes in promoting skin wound healing through activating PI3K/AKT pathway by PTEN.</p><p><strong>Methods and results: </strong>Human umbilical cord (HUC)-MSCs were infected with miR-150-5p overexpression and its control lentivirus, and HUC-MSCs-derived exosomes (MSCs-Exos) with stable expression of miR-150-5p were obtained. HaCaT cells were induced by H<sub>2</sub>O<sub>2</sub> to establish a cellular model of skin injury, in which the expression of miR-150-5p and PTEN and the phosphorylation of PI3K and AKT were evaluated. HaCaT cells were transfected with pcDNA3.1-PTEN or pcDNA3.1 and then cultured with normal exosomes or exosomes stably expressing miR-150-5p. Cell proliferation was inspected by CCK-8. Cell migration was detected by scratch test and cell apoptosis by flow cytometry. The starBase tool was used to predict the binding site of miR-150-5p to PTEN. Dual-luciferase reporter assay and RIP assay were applied to assess the interaction between miR-150-5p and PTEN. In H<sub>2</sub>O<sub>2</sub>-induced HaCaT cells, the miR-150-5p expression decreased, and PTEN expression increased in a concentration-dependent manner. MSCs-Exos promoted the growth and migration of H<sub>2</sub>O<sub>2</sub>-induced HaCaT cells and inhibited their apoptosis. In addition, overexpression of exosomal miR-150-5p enhanced the protective effect of MSCs-Exos on H<sub>2</sub>O<sub>2</sub>-induced HaCaT cells; PTEN overexpression in HaCaT cells partially restrained miR-150-5p-mediated inhibition on H<sub>2</sub>O<sub>2</sub>-induced injury in HaCaT cells. PTEN was a target gene of miR-150-5p. MiR-150-5p regulated PI3K/AKT pathway through PTEN.</p><p><strong>Conclusions: </strong>MSCs-derived miR-150-5p-expressing exosomes promote skin wound healing by activating PI3K/AKT pathway through PTEN.</p>","PeriodicalId":14392,"journal":{"name":"International journal of stem cells","volume":null,"pages":null},"PeriodicalIF":2.5000,"publicationDate":"2022-11-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/f7/65/ijsc-15-4-359.PMC9705155.pdf","citationCount":"6","resultStr":"{\"title\":\"MSCs-Derived miR-150-5p-Expressing Exosomes Promote Skin Wound Healing by Activating PI3K/AKT Pathway through PTEN.\",\"authors\":\"Cheng Xiu, Huining Zheng, Manfei Jiang, Jiaxu Li, Yanhong Zhou, Lan Mu, Weisong Liu\",\"doi\":\"10.15283/ijsc21135\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background and objectives: </strong>The goal of this study was to investigate the mechanism of mesenchymal stem cell (MSC)-derived microRNA (miR)-150-5p-expressing exosomes in promoting skin wound healing through activating PI3K/AKT pathway by PTEN.</p><p><strong>Methods and results: </strong>Human umbilical cord (HUC)-MSCs were infected with miR-150-5p overexpression and its control lentivirus, and HUC-MSCs-derived exosomes (MSCs-Exos) with stable expression of miR-150-5p were obtained. HaCaT cells were induced by H<sub>2</sub>O<sub>2</sub> to establish a cellular model of skin injury, in which the expression of miR-150-5p and PTEN and the phosphorylation of PI3K and AKT were evaluated. HaCaT cells were transfected with pcDNA3.1-PTEN or pcDNA3.1 and then cultured with normal exosomes or exosomes stably expressing miR-150-5p. Cell proliferation was inspected by CCK-8. Cell migration was detected by scratch test and cell apoptosis by flow cytometry. The starBase tool was used to predict the binding site of miR-150-5p to PTEN. Dual-luciferase reporter assay and RIP assay were applied to assess the interaction between miR-150-5p and PTEN. In H<sub>2</sub>O<sub>2</sub>-induced HaCaT cells, the miR-150-5p expression decreased, and PTEN expression increased in a concentration-dependent manner. MSCs-Exos promoted the growth and migration of H<sub>2</sub>O<sub>2</sub>-induced HaCaT cells and inhibited their apoptosis. In addition, overexpression of exosomal miR-150-5p enhanced the protective effect of MSCs-Exos on H<sub>2</sub>O<sub>2</sub>-induced HaCaT cells; PTEN overexpression in HaCaT cells partially restrained miR-150-5p-mediated inhibition on H<sub>2</sub>O<sub>2</sub>-induced injury in HaCaT cells. PTEN was a target gene of miR-150-5p. MiR-150-5p regulated PI3K/AKT pathway through PTEN.</p><p><strong>Conclusions: </strong>MSCs-derived miR-150-5p-expressing exosomes promote skin wound healing by activating PI3K/AKT pathway through PTEN.</p>\",\"PeriodicalId\":14392,\"journal\":{\"name\":\"International journal of stem cells\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":2.5000,\"publicationDate\":\"2022-11-30\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/f7/65/ijsc-15-4-359.PMC9705155.pdf\",\"citationCount\":\"6\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"International journal of stem cells\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.15283/ijsc21135\",\"RegionNum\":4,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2022/6/30 0:00:00\",\"PubModel\":\"Epub\",\"JCR\":\"Q3\",\"JCRName\":\"CELL & TISSUE ENGINEERING\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"International journal of stem cells","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.15283/ijsc21135","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2022/6/30 0:00:00","PubModel":"Epub","JCR":"Q3","JCRName":"CELL & TISSUE ENGINEERING","Score":null,"Total":0}
MSCs-Derived miR-150-5p-Expressing Exosomes Promote Skin Wound Healing by Activating PI3K/AKT Pathway through PTEN.
Background and objectives: The goal of this study was to investigate the mechanism of mesenchymal stem cell (MSC)-derived microRNA (miR)-150-5p-expressing exosomes in promoting skin wound healing through activating PI3K/AKT pathway by PTEN.
Methods and results: Human umbilical cord (HUC)-MSCs were infected with miR-150-5p overexpression and its control lentivirus, and HUC-MSCs-derived exosomes (MSCs-Exos) with stable expression of miR-150-5p were obtained. HaCaT cells were induced by H2O2 to establish a cellular model of skin injury, in which the expression of miR-150-5p and PTEN and the phosphorylation of PI3K and AKT were evaluated. HaCaT cells were transfected with pcDNA3.1-PTEN or pcDNA3.1 and then cultured with normal exosomes or exosomes stably expressing miR-150-5p. Cell proliferation was inspected by CCK-8. Cell migration was detected by scratch test and cell apoptosis by flow cytometry. The starBase tool was used to predict the binding site of miR-150-5p to PTEN. Dual-luciferase reporter assay and RIP assay were applied to assess the interaction between miR-150-5p and PTEN. In H2O2-induced HaCaT cells, the miR-150-5p expression decreased, and PTEN expression increased in a concentration-dependent manner. MSCs-Exos promoted the growth and migration of H2O2-induced HaCaT cells and inhibited their apoptosis. In addition, overexpression of exosomal miR-150-5p enhanced the protective effect of MSCs-Exos on H2O2-induced HaCaT cells; PTEN overexpression in HaCaT cells partially restrained miR-150-5p-mediated inhibition on H2O2-induced injury in HaCaT cells. PTEN was a target gene of miR-150-5p. MiR-150-5p regulated PI3K/AKT pathway through PTEN.
Conclusions: MSCs-derived miR-150-5p-expressing exosomes promote skin wound healing by activating PI3K/AKT pathway through PTEN.
期刊介绍:
International Journal of Stem Cells (Int J Stem Cells), a peer-reviewed open access journal, principally aims to provide a forum for investigators in the field of stem cell biology to present their research findings and share their visions and opinions. Int J Stem Cells covers all aspects of stem cell biology including basic, clinical and translational research on genetics, biochemistry, and physiology of various types of stem cells including embryonic, adult and induced stem cells. Reports on epigenetics, genomics, proteomics, metabolomics of stem cells are welcome as well. Int J Stem Cells also publishes review articles, technical reports and treatise on ethical issues.