MicroRNA-223 targets NLRP3 to relieve inflammation and alleviate spinal cord injury

Life Sci. 2020 Aug 1:254:117796. doi: 10.1016/j.lfs.2020.117796. Epub 2020 May 14.

Abstract

Aims: To explore the possible mechanism that microRNA-223 regulates the spinal cord injury as well as the posttranscriptional control of genes after spinal injury.

Materials and methods: Rats contusion spinal cord injury model and microglia model were established and examined by pathological test and the inflammatory cytokines levels were evaluated by RT-PCR. Then microRNA-223 was overexpressed in spinal cord to see the impact on rats with spinal cord injury. The overexpression of microRNA-223 in microglia stimulated by LPS was used to assess the inflammation. Then bioinformatic method combined with luciferase reporter genes were used to detect the target gene of microRNA-223. Then NLRP3, one of the target genes of microRNA-223 were regulated to see the impact on microglia as well as spinal injury rats.

Key findings: It showed that microRNA-223 increased after acute spinal injury. However, the suppression of microRNA-223 aggravated the spinal injury as well as the inflammation while the over-expression of microRNA-223 alleviated the spinal injury to some extent, decreased the inflammation and improved nervous system function. In vitro, it was found that the over-expression of microRNA-223 in microglia suppressed inflammation induced by LPS and vice versa. NLRP3 was found the target of microRNA-223. The up-regulation of NLRP3 could diminish the effects of microRNA-223 and aggravated inflammation in microglia.

Significance: The over-expression of microRNA-223 alleviated the inflammation and improved neuron function. NLRP3 was the downstream target of microRNA-223, the overexpression of which led to severe inflammation in microglia.

Keywords: Inflammation; Microglia; NLRP3; Spinal cord injury; microRNA-223.

MeSH terms

  • Animals
  • Cytokines / metabolism
  • Inflammation / complications
  • Inflammation / prevention & control*
  • Lipopolysaccharides
  • MicroRNAs / biosynthesis
  • MicroRNAs / physiology*
  • Microglia / metabolism
  • NLR Family, Pyrin Domain-Containing 3 Protein / genetics
  • NLR Family, Pyrin Domain-Containing 3 Protein / physiology*
  • Primary Cell Culture
  • Rats
  • Spinal Cord Injuries / complications
  • Spinal Cord Injuries / metabolism
  • Spinal Cord Injuries / pathology
  • Spinal Cord Injuries / physiopathology*

Substances

  • Cytokines
  • Lipopolysaccharides
  • MIRN223 microRNA, rat
  • MicroRNAs
  • NLR Family, Pyrin Domain-Containing 3 Protein
  • Nlrp3 protein, rat