Title: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
Volume: 19
Issue: 5
Author(s): Hongnan Li, Weidong Lin, Yunlei Li, Jiayang Zhang, Runsheng Liu, Minghai Qu, Ruihua Wang, Xiaomin Kang and Xuekun Xing*
Affiliation:
- Department of Public Health, Guilin Medical University, Guilin Guangxi, 541104, China.
- Guangxi Key Laboratory of Environmental Exposomics and Entire Lifecycle Health Research, Guilin Medical
University, Guilin Guangxi, 541199, China
Keywords:
miR-27b-3p, SMAD4, BMSC-EVs, Wnt/β-catenin, apoptosis.
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.
