MiR-195-5p represses inflammation, apoptosis, oxidative stress, and endoplasmic reticulum stress in sepsis-induced myocardial injury by targeting activating transcription factor 6

Cell Biol Int. 2022 Feb;46(2):243-254. doi: 10.1002/cbin.11726. Epub 2021 Dec 2.

Abstract

Myocardial injury (MI) is a common complication of sepsis. MicroRNAs (miRNAs) have been suggested as potential biomarkers of MI; however, their mechanisms in sepsis-induced MI remain unclear. A sepsis rat model was constructed by use of cecal ligation and puncture (CLP). The levels of miR-195-5p and activating transcription factor 6 (ATF6) expression were determined by quantitative reverse-transcription polymerase chain reaction, and cytokine levels were detected by ELISA. The levels of oxidative stress (OS)-related indicators and endoplasmic reticulum stress (ERS)-related proteins were examined, and the regulatory effect of miR-195-5p on ATF6 was determined by using the luciferase reporter assay. Our results showed that miR-195-5p expression was downregulated and ATF6 expression was upregulated in lipopolysaccharide-induced cardiomyocytes and mice with CLP-induced sepsis. We also found that miR-195-5p could markedly attenuate the inflammation, apoptosis, OS, and ERS associated with sepsis-induced MI. Additionally, we verified that miR-195-5p could relieve sepsis-induced MI by targeting ATF6. This study identified potential targets for treating MI after sepsis.

Keywords: activating transcription factor 6; endoplasmic reticulum stress; miR-195-5p; myocardial injury; sepsis.

MeSH terms

  • Activating Transcription Factor 6 / metabolism
  • Activating Transcription Factor 6 / pharmacology
  • Animals
  • Apoptosis
  • Endoplasmic Reticulum Stress
  • Inflammation / metabolism
  • Mice
  • MicroRNAs* / genetics
  • MicroRNAs* / metabolism
  • Oxidative Stress
  • Rats
  • Sepsis* / complications
  • Sepsis* / metabolism

Substances

  • Activating Transcription Factor 6
  • Atf6 protein, mouse
  • Atf6 protein, rat
  • MIRN195a microRNA, mouse
  • MIRN195 microRNA, rat
  • MicroRNAs