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Exosomal miR-192-5p secreted by bone marrow mesenchymal stem cells inhibits hepatic stellate cell activation and targets PPP2R3A

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机构: [1]Department of Gastroenterology, Wuhan Third Hospital, Tongren Hospital of Wuhan University, Wuhan, China.
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关键词: Hepatic fibrosis extracellular vehicles BMSC hepatic stellate cells miR-192-5p

摘要:
Bone marrow mesenchymal stem cell (BSMC)-derived extracellular vehicles (EVs) have a pivotal therapeutic potential in hepatic fibrosis (HF). Activation of hepatic stellate cells (HSCs) is the key mechanism in HF progression. Downregulation of miR-192-5p was previously observed in activated HSCs. Nonetheless, the functions of BSMC-derived exosomal miR-192-5p in activated HSCs remain unclear. In this study, transforming growth factor (TGF)-β1 was used to activate HSC-T6 cells to mimic HF in vitro. Characterization of BMSCs and BMSC-derived EVs was performed. Cell-counting kit-8 assay, flow cytometry, and western blotting revealed that TGF-β1 increased cell viability, promoted cell cycle progression, and induced upregulation of fibrosis markers in HSC-T6 cells. Overexpression of miR-192-5p or BMSC-derived exosomal miR-192-5p suppressed TGF-β1-triggered HSC-T6 cell activation. RT-qPCR revealed that protein phosphatase 2 regulatory subunit B'' alpha (PPP2R3A) was downregulated in miR-192-5p-overexpressed HSC-T6 cells. Luciferase reporter assay was used for verifying the relation between miR-192-5p and PPP2R3A, which showed that miR-192-5p targeted PPP2R3A in activated HSC-T6 cells. Collectively, BMSC-derived exosomal miR-192-5p targets PPP2R3A and inhibits activation of HSC-T6 cells.

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出版当年[2022]版:
大类 | 4 区 生物学
小类 | 4 区 细胞生物学
最新[2023]版:
大类 | 4 区 生物学
小类 | 4 区 细胞生物学
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出版当年[2021]版:
Q4 CELL BIOLOGY
最新[2023]版:
Q4 CELL BIOLOGY

影响因子: 最新[2023版] 最新五年平均 出版当年[2021版] 出版当年五年平均 出版前一年[2020版] 出版后一年[2022版]

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第一作者机构: [1]Department of Gastroenterology, Wuhan Third Hospital, Tongren Hospital of Wuhan University, Wuhan, China.
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通讯机构: [1]Department of Gastroenterology, Wuhan Third Hospital, Tongren Hospital of Wuhan University, Wuhan, China. [*1]Department of Gastroenterology, Wuhan Third Hospital, Tongren Hospital of Wuhan University, No. 241 Pengliuyang Road, Wuchang District, Wuhan, Hubei, China
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