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.
基金:
Wuhan Health and Wellness Committee in 2021 (Approval number: WX21D19).
第一作者机构:[1]Department of Gastroenterology, Wuhan Third Hospital, Tongren Hospital of Wuhan University, Wuhan, China.
共同第一作者:
通讯作者:
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
推荐引用方式(GB/T 7714):
Tan Jie,Chen Mingtao,Liu Meng,et al.Exosomal miR-192-5p secreted by bone marrow mesenchymal stem cells inhibits hepatic stellate cell activation and targets PPP2R3A[J].JOURNAL OF HISTOTECHNOLOGY.2023,46(4):158-169.doi:10.1080/01478885.2023.2215151.
APA:
Tan Jie,Chen Mingtao,Liu Meng,Chen Aifang,Huang Min...&Chen Wei.(2023).Exosomal miR-192-5p secreted by bone marrow mesenchymal stem cells inhibits hepatic stellate cell activation and targets PPP2R3A.JOURNAL OF HISTOTECHNOLOGY,46,(4)
MLA:
Tan Jie,et al."Exosomal miR-192-5p secreted by bone marrow mesenchymal stem cells inhibits hepatic stellate cell activation and targets PPP2R3A".JOURNAL OF HISTOTECHNOLOGY 46..4(2023):158-169