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

Chi,Xiaobin; Jiang,Yi; Chen,Yongbiao; Yang,Fang; Cai,Qiucheng; Pan,Fan; Lv,Lizhi; Zhang,Xiaojin

doi:10.3892/mmr.2019.10645

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

Authors:
- Xiaobin Chi
- Yi Jiang
- Yongbiao Chen
- Fang Yang
- Qiucheng Cai
- Fan Pan
- Lizhi Lv
- Xiaojin Zhang
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Affiliations: Department of Hepatobiliary Surgery, Fuzong Clinical Medical College of Fujian Medical University, Fuzhou, Fujian 350001, P.R. China, Department of Hepatobiliary Surgery, 900 Hospital of The Joint Logistics Team, Fuzhou, Fujian 350025, P.R. China
Published online on: September 3, 2019 https://doi.org/10.3892/mmr.2019.10645
Pages: 4003-4012

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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.

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