Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, P.R. China.
Department of Emergency, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, P.R. China.
Mol Med Rep. 2021 Sep;24(3). doi: 10.3892/mmr.2021.12314. Epub 2021 Jul 23.
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 and . 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 and cell injury . 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.
缺血/再灌注(I/R)诱导的肝损伤仍然是肝移植和肝切除术的主要关注点。先前的研究表明,microRNAs(miRs)参与多种病理生理过程,包括肝 I/R。据报道,miR-140-5p 可抑制几种疾病中的炎症反应和细胞凋亡;然而,miR-140-5p 在肝 I/R 中的作用尚不清楚。本研究旨在探讨 miR-140-5p 在肝 I/R 损伤中的潜在作用和机制。建立了小鼠肝 I/R 和小鼠 AML12 细胞缺氧/复氧(H/R)模型。使用 miR-140-5p 模拟物、抑制剂或激动剂过表达或抑制 miR-140-5p 。采用逆转录-定量聚合酶链反应检测 miR-140-5p 表达。采用多种生化测定法评估肝和细胞损伤。采用双荧光素酶报告基因检测法证实 miR-140-5p 与钙蛋白酶-1(CAPN1)之间的关联。结果显示,在小鼠肝 I/R 损伤模型和 H/R 处理的 AML12 细胞中,miR-140-5p 表达降低,而过表达 miR-140-5p 可减轻肝损伤 和细胞损伤 。此外,CAPN1 被确定为 miR-140-5p 的靶标;过表达 CAPN1 可消除 miR-140-5p 对 H/R 诱导的细胞损伤的作用。本研究表明,miR-140-5p 通过靶向 CAPN1 保护肝脏免受 I/R 损伤,这可能为肝脏 I/R 损伤提供新的治疗靶点。