Bone Marrow Mesenchymal Stem Cell Extracellular Vesicle-derived miR-27b-3p activates the Wnt/Β-catenin Pathway by Targeting SMAD4 and Aggravates Hepatic Ischemia-reperfusion Injury

文献类型： 外文期刊

第一作者： Li, Hongnan

作者： Li, Hongnan;Zhang, Jiayang;Liu, Runsheng;Qu, Minghai;Wang, Ruihua;Kang, Xiaomin;Xing, Xuekun;Lin, Weidong;Li, Yunlei;Xing, Xuekun

作者机构：

关键词： miR-27b-3p; SMAD4; BMSC-EVs; Wnt/beta-catenin; apoptosis

期刊名称：CURRENT STEM CELL RESEARCH & THERAPY （ 影响因子：2.7； 五年影响因子：3.3 ）

ISSN： 1574-888X

年卷期： 2024 年 19 卷 5 期

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收录情况： SCI

摘要： Background: To investigate the roles of extracellular vesicles (EVs) secreted from bone marrow mesenchymal stem cells (BMSCs) and miR-27 (highly expressed in BMSC EVs) in hepatic ischemia-reperfusion injury (HIRI). Approaches and Results: We constructed a HIRI mouse model and pretreated it with an injection of agomir-miR-27-3p, agomir-NC, BMSC-EVs or control normal PBS into the abdominal cavity. Compared with the HIRI group, HIRI mice preinjected with BMSC-EVs had significantly decreased alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels and alleviated liver necrosis (P<0.05). However, compared with HIRI+NC mice, HIRI+miR-27b mice had significantly increased ALT and AST levels, aggravated liver necrosis, and increased apoptosis-related protein expression (P<0.05). The proliferation and apoptosis of AML-12 cells transfected with miR-27 were significantly higher than the proliferation and apoptosis of AML-12 cells in the mimic NC group (P<0.01) after hypoxia induction. SMAD4 was proven to be a miR-27 target gene. Furthermore, compared to HIRI+NC mice, HIRI+miR-27 mice displayed extremely reduced SMAD4 expression and increased levels of wnt1, beta-catenin, c-Myc, and Cyclin D1. Conclusion: Our findings reveal the role and mechanism of miR-27 in HIRI and provide novel insights for the prevention and treatment of HIRI; for example, EVs derived from BMSCs transfected with antimiR-27 might demonstrate better protection against HIRI.

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