Suppression of microRNA‑27a protects against liver ischemia/reperfusion injury by targeting PPARγ and inhibiting endoplasmic reticulum stress.

Abstract

Liver ischemia‑reperfusion (I/R) injury is an important clinical issue related to liver transplantation. Recent studies suggest that microRNAs are implicated in various biological and pathological processes, including liver I/R injury. This study aimed to investigate the role and potential mechanism of miR‑27a during liver I/R injury. A liver I/R model was induced via 60 min of ischemia and reperfusion for 6 h in rats. Cells were transfected with miR‑27a mimics or the miR‑27a inhibitor to examine the effect of miR‑27a on liver I/R. Apoptotic cells were detected by flow cytometry and TUNEL staining. The expression of miR‑27a was measured by real‑time PCR. The expression of peroxisome proliferator‑activated receptor γ (PPARγ); gastrin‑releasing peptide 78 (GRP78) and C/EBP homologous protein (CHOP) were detected by western blot analysis. The results showed that miR‑27a was significantly upregulated during I/R injury in vivo and in vitro. In addition, miR‑27a inhibitors attenuated hypoxia/reoxygenation (H/R)‑induced oxidative stress, endoplasmic reticulum stress (ERS) and apoptosis in AML12 cells. By contrast, miR‑27a mimics promoted hypoxia/reoxygenation‑induced ERS, and apoptosis. Furthermore, PPARγ was identified as a target gene of miR‑27a using bioinformatic analysis and a dual‑luciferase reporter assay. Knockdown of PPARγ significantly abrogated the inhibitory effect of miR‑27a inhibitors on the ERS pathway. Moreover, the miR‑27a antagomir attenuated liver I/R injury in rats, a finding manifested by reduced ALT/AST, hepatocyte apoptosis, oxidative stress and inhibition of the ERS pathway. Taken together, these findings demonstrate that suppression of miR‑27a protects against liver I/R injury by targeting PPARγ and by inhibiting the ERS pathway.