miR1405p alleviates mouse liver ischemia/reperfusion injury by targeting CAPN1

Qiwen Yu1, Sanyang Chen2, Hongwei Tang1

  • 1Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, P.R. China.

Insights

MicroRNA-140-5p protects against liver ischemia/reperfusion (I/R) injury by targeting calpain-1. This finding offers a potential new therapeutic strategy for liver I/R damage.

Area of Science:

  • Molecular Biology
  • Hepatology
  • Biochemistry

Background:

  • Ischemia/reperfusion (I/R)-induced liver injury is a significant clinical challenge in liver transplantation and surgery.
  • MicroRNAs (miRs) are implicated in various pathophysiological processes, including liver I/R injury, but the specific role of miR-140-5p is not well understood.

Purpose of the Study:

  • To investigate the role and underlying mechanism of miR-140-5p in liver I/R injury.
  • To determine if miR-140-5p can serve as a therapeutic target for mitigating liver I/R damage.

Main Methods:

  • Established mouse models of liver I/R and AML12 cell hypoxia/reoxygenation (H/R).
  • Utilized miR-140-5p mimics and inhibitors for in vitro and in vivo manipulation.
  • Quantified miR-140-5p expression using RT-qPCR and assessed liver/cell injury via biochemical assays.
  • Confirmed the interaction between miR-140-5p and calpain-1 (CAPN1) using a dual-luciferase reporter assay.

Main Results:

  • miR-140-5p expression was significantly downregulated in liver I/R and H/R models.
  • Overexpression of miR-140-5p ameliorated liver and cell injury in both in vivo and in vitro settings.
  • Calpain-1 (CAPN1) was identified as a direct target of miR-140-5p.
  • Upregulation of CAPN1 reversed the protective effects of miR-140-5p against H/R-induced cell injury.

Conclusions:

  • miR-140-5p exerts a protective effect against liver I/R injury.
  • This protective mechanism involves the targeting of calpain-1 (CAPN1).
  • miR-140-5p represents a promising therapeutic target for managing liver I/R injury.

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