Up-regulation of miR-146b-3p protects septic mice with acute respiratory distress syndrome by inhibiting PI3K/AKT signaling pathway

J Bioenerg Biomembr. 2020 Aug;52(4):229-236. doi: 10.1007/s10863-020-09839-3. Epub 2020 Jun 2.

Abstract

This study aimed to explore the role of miR-146b-3p in acute respiratory distress syndrome in septic mice. Ten mice were randomly selected as normal group (n = 10, without any treatment) and 60 septic mice with acute respiratory distress syndrome were divided into model group (n = 10, without any treatment), negative control (NC) mimic group (n = 10, injected with NC mimic), miR-146b-3p mimic group (n = 10, injected with miR-146b-3p mimic), si-NC group (n = 10, injected with PI3Kγ siRNA NC), si-PI3Kγ group (n = 10, injected with PI3Kγ silencing plasmid), and miR-146b-3p mimic + oe-PI3Kγ group (n = 10, injected with miR-146b-3p mimic + PI3Kγ overexpression plasmid). We found that miR-146b-3p negatively regulated PI3Kγ. Compared with normal group, model mice had decreased expression of miR-146b-3p, increased expressions of PI3Kγ, p-AKT, ASC, NLRP3 and Caspase-1 proteins, higher W/D ratio, and more serum IL-1β and IL-18 content (all P < 0.05). All indicators in miR-146b-3p mimic group and si-PI3Kγ group were significantly improved as compared to model group (all P < 0.05). Over-expression of PI3Kγ could weaken the treatment effect of miR-146b-3p mimic in model mice. Therefore, up-regulation of miR-146b-3p can inhibit PI3K/AKT signaling pathway to improve acute respiratory distress syndrome in septic mice.

Keywords: Acute respiratory distress syndrome; PI3K/AKT; Sepsis; miR-146b-3p.

MeSH terms

  • Animals
  • Mice
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • Phosphatidylinositol 3-Kinases / metabolism*
  • Proto-Oncogene Proteins c-akt / metabolism*
  • Respiratory Distress Syndrome / genetics
  • Respiratory Distress Syndrome / metabolism*
  • Sepsis / genetics
  • Sepsis / metabolism*
  • Signal Transduction
  • Up-Regulation

Substances

  • MicroRNAs
  • Proto-Oncogene Proteins c-akt