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

被引:2
作者
Li, Hongnan [1 ]
Lin, Weidong [2 ]
Li, Yunlei [3 ]
Zhang, Jiayang [1 ]
Liu, Runsheng [1 ]
Qu, Minghai [1 ]
Wang, Ruihua [1 ]
Kang, Xiaomin [1 ]
Xing, Xuekun [1 ,4 ]
机构
[1] Guilin Med Univ, Dept Publ Hlth, Guilin 541104, Guangxi, Peoples R China
[2] Shanghai Jiao Tong Univ, Sch Med, Shanghai 200025, Peoples R China
[3] Chinese Acad Agr Sci, Minist Agr & Rural Affairs, Inst Anim Sci, Key Lab Anim Poultry Genet Breeding & Reprod, Beijing 100193, Peoples R China
[4] Guilin Med Univ, Guangxi Key Lab Environm Expos & Entire Lifecycle, Guilin 541199, Guangxi, Peoples R China
关键词
miR-27b-3p; SMAD4; BMSC-EVs; Wnt/beta-catenin; apoptosis; BREAST-CANCER; LIVER; PROLIFERATION; MIGRATION; EXOSOMES;
D O I
10.2174/1574888X19666230901140628
中图分类号
Q813 [细胞工程];
学科分类号
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.
引用
收藏
页码:755 / 766
页数:12
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