miRNA-144 induces microglial autophagy and inflammation following intracerebral hemorrhage

Immunol Lett. 2017 Feb:182:18-23. doi: 10.1016/j.imlet.2017.01.002. Epub 2017 Jan 3.

Abstract

Autophagic activation mediated inflammation contributes to brain injury of intracerebral hemorrhage (ICH). MiRNAs play a key role in inflammation, which negatively and posttranscriptionally regulate gene expression and function. Modulating the mTOR signal, a central regulator of autophagy, could be of great significance for ICH. However, the specific of miRNA is unknown. In the current study, we detected the miRNA-144 expression, autophagic activity and inflammation of microglia in ICH. We also knocked down endogenous miRNA-144 to regulate autophagy and inflammation in ICH. In addition, we assessed the neurological damge in ICH mice. We found that ICH promoted miRNA-144 expression but downregulated mTOR expression. In addition, upregulation of mTOR attenuated microglial autophagy and inflammation in ICH. Furthermore, downregulation of miRNA-144 also inhibited inflammation, brain edema and improved neurological functions in ICH mice. Taken together, our findings suggested that miRNA-144 was a crucial regulator of autophagy via regulation of mTOR, and represented a promising therapeutical strategy for ICH.

Keywords: Autophagy; ICH; Inflammation; Microglia; miRNA-144.

MeSH terms

  • Animals
  • Autophagy / genetics*
  • Cerebral Hemorrhage / complications*
  • Cerebral Hemorrhage / etiology
  • Cerebral Hemorrhage / metabolism
  • Cerebral Hemorrhage / pathology
  • Gene Expression
  • Inflammation / etiology*
  • Inflammation / metabolism
  • Inflammation / pathology
  • Mice
  • MicroRNAs / genetics*
  • Microglia / metabolism*
  • Microglia / pathology
  • Microglia / ultrastructure
  • TOR Serine-Threonine Kinases / metabolism

Substances

  • MIRN144 microRNA, mouse
  • MicroRNAs
  • TOR Serine-Threonine Kinases