miR‑140‑5p alleviates mouse liver ischemia/reperfusion injury by targeting CAPN1

miR-140-5p 通过靶向 CAPN1 减轻小鼠肝脏缺血/再灌注损伤

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作者:Qiwen Yu, Sanyang Chen, Hongwei Tang, Han Yang, Jiakai Zhang, Xiaoyi Shi, Jie Li, Wenzhi Guo, Shuijun Zhang

Abstract

Ischemia/reperfusion (I/R)‑induced liver injury remains a primary concern in liver transplantation and hepatectomy. Previous studies have indicated that microRNAs (miRs) are involved in multiple pathophysiological processes, including liver I/R. miR‑140‑5p reportedly inhibits inflammatory responses and apoptosis in several diseases; however, the role of miR‑140‑5p in liver I/R remains unknown. The present study aimed to investigate the potential role and mechanism of miR‑140‑5p on liver I/R injury. Mouse liver I/R and mouse AML12 cell hypoxia/reoxygenation (H/R) models were established. miR‑140‑5p mimics, inhibitor or agonists were used to overexpress or inhibit miR‑140‑5p in vitro and in vivo. Reverse transcription‑quantitative polymerase chain reaction was used to detect miR‑140‑5p expression. Liver and cell injury were evaluated using several biochemical assays. The association between miR‑140‑5p and calpain‑1 (CAPN1) was confirmed using a dual‑luciferase reporter assay. The results revealed that miR‑140‑5p expression was decreased in the mouse model of liver I/R injury and AML12 cells subjected to H/R, while overexpressed miR‑140‑5p reduced liver injury in vivo and cell injury in vitro. In addition, CAPN1 was determined to be a target of miR‑140‑5p; overexpressed CAPN1 abrogated the effect of miR‑140‑5p on H/R‑induced cell injury. The present study indicated that miR‑140‑5p protected against liver I/R by targeting CAPN1, which may provide a novel therapeutic target for liver I/R injury.

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