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

• Published in: Current stem cell research & therapy Vol. 19; no. 5; p. 755
• Main Authors: Li, Hongnan, Lin, Weidong, Li, Yunlei, Zhang, Jiayang, Liu, Runsheng, Qu, Minghai, Wang, Ruihua, Kang, Xiaomin, Xing, Xuekun
• Format: Journal Article
• Language: English
• Published: United Arab Emirates 01.01.2024
• Subjects: Animals; beta Catenin - genetics; beta Catenin - metabolism; Extracellular Vesicles - metabolism; Leukemia, Myeloid, Acute - metabolism; Liver - metabolism; Mesenchymal Stem Cells - metabolism; Mice; MicroRNAs - genetics; MicroRNAs - metabolism; Necrosis; Reperfusion Injury - genetics; apoptosis; SMAD4; miR-27b-3p; BMSC-EVs; Wnt/β-catenin
• ISSN: 2212-3946
• DOI: 10.2174/1574888X19666230901140628

To investigate the roles of extracellular vesicles (EVs) secreted from bone marrow mesenchymal stem cells (BMSCs) and (highly expressed in BMSC EVs) in hepatic ischemia‒ reperfusion injury (HIRI). We constructed a HIRI mouse model and pretreated it with an injection of agomir- , 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+ 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 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 target gene. Furthermore, compared to HIRI+NC mice, HIRI+ mice displayed extremely reduced SMAD4 expression and increased levels of wnt1, β-catenin, c-Myc, and Cyclin D1. Our findings reveal the role and mechanism of in HIRI and provide novel insights for the prevention and treatment of HIRI; for example, EVs derived from BMSCs transfected with might demonstrate better protection against HIRI.