miR-214-3p Attenuates Sepsis-Induced Myocardial Dysfunction in Mice by Inhibiting Autophagy through PTEN/AKT/mTOR Pathway

Biomed Res Int. 2020 Jul 2:2020:1409038. doi: 10.1155/2020/1409038. eCollection 2020.

Abstract

Aims. More than half of the patients with sepsis would develop cardiac dysfunction, which is termed as sepsis-induced myocardial dysfunction (SIMD). Previous studies suggest that autophagy may play an important role in SIMD. The present study investigated whether miR-214-3p could attenuate SIMD by inhibiting autophagy. Main Methods. In this article, we investigated the role of autophagy in a mouse model of cecal ligation and puncture (CLP). The structure and function of hearts harvested from the mice were evaluated. Myocardial autophagy levels were detected with immunohistochemical, immunofluorescent, and Western blot. Key Findings. miR-214-3p can alleviate SIMD in septic mice by inhibiting the level of cardiac autophagy to attenuate myocardial dysfunction. Moreover, this study showed that miR-214-3p inhibited autophagy by silencing PTEN expression in the myocardial tissues of septic mice. Significance. This study showed that miR-214-3p attenuated SIMD through myocardial autophagy inhibition by silencing PTEN expression and activating the AKT/mTOR pathway. The present findings supported that miR-214-3p may be a potential therapeutic target for SIMD.

MeSH terms

  • Animals
  • Autophagy / genetics*
  • Cecum / pathology
  • Heart / physiopathology*
  • Ligation
  • Male
  • Mice
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • Microtubule-Associated Proteins / metabolism
  • Myocardium / pathology
  • Myocardium / ultrastructure
  • NLR Family, Pyrin Domain-Containing 3 Protein / metabolism
  • PTEN Phosphohydrolase / metabolism*
  • Proto-Oncogene Proteins c-akt / metabolism*
  • Punctures
  • STAT3 Transcription Factor / metabolism
  • Sepsis / complications*
  • Sequestosome-1 Protein / metabolism
  • Signal Transduction*
  • TOR Serine-Threonine Kinases / metabolism*
  • Up-Regulation

Substances

  • Map1lc3b protein, mouse
  • MicroRNAs
  • Microtubule-Associated Proteins
  • Mirn214 microRNA, mouse
  • NLR Family, Pyrin Domain-Containing 3 Protein
  • Nlrp3 protein, mouse
  • STAT3 Transcription Factor
  • Sequestosome-1 Protein
  • Sqstm1 protein, mouse
  • Proto-Oncogene Proteins c-akt
  • TOR Serine-Threonine Kinases
  • PTEN Phosphohydrolase