BMSC-exosomes miR-25-3p Regulates the p53 Signaling Pathway Through PTEN to Inhibit Cell Apoptosis and Ameliorate Liver Ischemia-reperfusion Injury

文献类型： 外文期刊

第一作者： Li, Hongnan

作者： Li, Hongnan;Liu, Runsheng;Qu, Minghai;Zhang, Jiayang;Xing, Xuekun;Lin, Weidong;Zhang, Guangzhi;Xing, Xuekun

作者机构：

关键词： HIRI; BMSC Exosomes; miR-25b-3p; PTEN; p53; Apoptosis

期刊名称：STEM CELL REVIEWS AND REPORTS （ 影响因子：4.8； 五年影响因子：4.7 ）

ISSN： 2629-3269

年卷期： 2023 年

页码：

收录情况： SCI

摘要： Background Hepatic ischemia-reperfusion injury (HIRI) is a pathological phenomenon during liver surgery, and bone marrow-mesenchymal stem cell (BMSC) exosomes (BMSC-Exos) regulate cell apoptosis and reduce ischemia-reperfusion injury. We aimed to investigate the roles of BMSC-Exos and miR-25b-3p (enriched in BMSC-Exos) in HIRI and elucidate the underlying mechanisms.Approaches and Results An HIRI mouse model was constructed and preinjected with BMSC-Exos, agomir-miR-25, agomir-miR-NC, or PBS via the tail vein. Compared with mice with HIRI, mice with HIRI preinjected with BMSC-Exos had significantly decreased alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels and alleviated liver necrosis (P < 0.05). Quantitative hepatic transcriptomics showed that mice with HIRI preinjected with BMSC-Exos exhibited increased cell division, hematopoietic or lymphoid organ development and metabolic processes. miRNA sequencing of BMSC-Exos revealed that miR-25, which is related to I/R injury, was enriched in the exosomes. Compared with HIRI + NC mice, HIRI + miR-25b-3p mice had significantly increased miR-25b-3p expression, decreased ALT/AST levels and apoptosis-related protein expression (P < 0.05), and alleviated liver necrosis. The proliferation of AML-12 cells transfected with miR-25b-3p was significantly higher than that in the mimic NC group (P < 0.01) after hypoxia induction, and the apoptosis rate of cells was significantly lower than that in the NC group (P < 0.01). PTEN was identified as a miR-25b-3p target gene. PTEN expression was significantly diminished in miR-25b-3p-transfected AML12 cells (P < 0.05). HIRI + agomir-miR-25 mice displayed reduced PTEN expression and decreased p53 and cleaved caspase 3 levels compared to HIRI + NC mice.Conclusions We revealed the roles and underlying mechanisms of BMSC-Exos and miR-25 in HIRI, contributing to the prevention and treatment of HIRI.

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