circ-AKT3 aggravates renal ischaemia-reperfusion injury via regulating miR-144-5p /Wnt/β-catenin pathway and oxidative stress

J Cell Mol Med. 2022 Mar;26(6):1766-1775. doi: 10.1111/jcmm.16072. Epub 2020 Nov 16.

Abstract

Renal ischaemia-reperfusion (RI/R) injury is one major pathological state of acute kidney injury (AKI) with a mortality rate ranking 50% to 80%. MiR-144-5p acts as a molecular trigger in various diseases. We presumed that miR-144-5p might be involved RI/R injury progression. We found that RI/R injury decreased miR-144-5p expression in rat models. MiR-144-5p downregulation promoted cell apoptosis rate and activated Wnt/β-catenin signal in RI/R injury rats. By performing bioinformatic analysis, RIP, RNA pull-down, luciferase reporter experiments, we found that circ-AKT3 sponged to miR-144-5p and decreased its expression in RI/R injury rats. Moreover, we found that circ-AKT3 promoted cell apoptosis rate and activated Wnt/β-catenin signal, and miR-144-5p mimic reversed the promotive effect of circ-AKT3 in rat models. We also found that circ-AKT3 increased the oxidative stress level in rat models. In conclusion, our study suggests that the circAKT3 is involved RI/R injury progression through regulating miR-144-5p/Wnt/β-catenin pathway and oxidative stress.

Keywords: Wnt/β-catenin signal; circ-AKT3; circRNA; miR-144-5p; oxidative stress; renal ischaemia-reperfusion injury.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis / genetics
  • MicroRNAs* / metabolism
  • Oxidative Stress / genetics
  • Proto-Oncogene Proteins c-akt / metabolism
  • RNA, Circular / genetics
  • Rats
  • Reperfusion Injury* / genetics
  • beta Catenin / genetics
  • beta Catenin / metabolism

Substances

  • MIRN144 microRNA, rat
  • MicroRNAs
  • RNA, Circular
  • beta Catenin
  • Akt3 protein, rat
  • Proto-Oncogene Proteins c-akt