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


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Abstract

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, β-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.

About the authors

Hongnan Li

Department of Public Health, Guilin Medical University

Email: info@benthamscience.net

Weidong Lin

School of Medicine, Shanghai Jiao Tong University

Email: info@benthamscience.net

Yunlei Li

Key Laboratory of Animal (Poultry) Genetics Breeding and Reproduction, Ministry of Agriculture and Rural Affairs, Institute of Animal Science, Chinese Academy of Agricultural Sciences

Email: info@benthamscience.net

Jiayang Zhang

Department of Public Health, Guilin Medical University

Email: info@benthamscience.net

Runsheng Liu

Department of Public Health, Guilin Medical University

Email: info@benthamscience.net

Minghai Qu

Department of Public Health, Guilin Medical University

Email: info@benthamscience.net

Ruihua Wang

Department of Public Health, Guilin Medical University

Email: info@benthamscience.net

Xiaomin Kang

Department of Public Health, Guilin Medical University

Email: info@benthamscience.net

Xuekun Xing

Department of Public Health, Guilin Medical University

Author for correspondence.
Email: info@benthamscience.net

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