Downregulation of miR-497-5p prevents liver ischemia-reperfusion injury in association with MED1/TIMP-2 axis and the NF-κB pathway

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-kappa B) 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.

Automated summary

Liver ischemia-reperfusion (I/R) injury is a common pathological phenomenon with unclear mechanisms. This study focused on the role of miR-497b-5p in liver I/R injury, showing its involvement in regulating inflammatory factors and cell apoptosis. Additionally, miR-497b-5p may activate the NF-κB pathway to promote liver I/R injury, while the overexpression of MED1 and TIMP2 could alleviate the damage.