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Downregulation of miR‐497‐5p prevents liver ischemia‐reperfusion injury in association with MED1/TIMP‐2 axis and the NF‐κB pathway
Author(s) -
Wu Kun,
Tao Guoquan,
Xu Ting,
An Yuanyuan,
Yu Xiangyou,
Wang Yi,
Wang Shaochuang,
Guo Wen,
Ma Long
Publication year - 2021
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.202001029r
Subject(s) - downregulation and upregulation , nf κb , association (psychology) , reperfusion injury , chemistry , medicine , ischemia , microbiology and biotechnology , signal transduction , biology , biochemistry , gene , psychology , psychotherapist
Liver ischemia‐reperfusion (I/R) injury is a common clinical pathological phenomenon, which is accompanied by the occurrence in liver transplantation. However, the underlying mechanism is not yet fully understood. MicroRNAs (miRNAs) play an important role in liver I/R injury. Therefore, the study of miRNAs function will contribute a new biological marker diagnosis of liver I/R injury. This study aims to evaluate effects of miR‐497‐5p in liver I/R injury in mice. The related regulatory factors of miR‐497‐5p in liver I/R injury were predicted by bioinformatics analysis. Vascular occlusion was performed to establish the liver I/R injury animal models. Hypoxia/reoxygenation (H/R) was performed to establish the in vitro models. Hematoxylin‐eosin (HE) staining was conducted to assess liver injury. The inflammatory factors were evaluated by enzyme‐linked immunosorbent assay (ELISA). Flow cytometry was adopted to assess the cell apoptosis. The expression of miR‐497b‐5p was increased in liver I/R injury. Knockdown of miR‐497b‐5p inhibited the production of inflammatory factors and cell apoptosis. Overexpression of mediator complex subunit 1 (MED1) and tissue inhibitor of metalloproteinase 2 (TIMP2) inhibited cell apoptosis to alleviate liver I/R injury. miR‐497b‐5p could activate the nuclear factor kappa‐B (NF‐κB) pathway by inhibiting the MED1/TIMP‐2 axis to promote liver I/R injury. This study may provide a new strategy for the treatment of liver I/R injury.