Hypoxia inducible factor-1 (HIF-1α) reduced inflammation in spinal cord injury via miR-380-3p/ NLRP3 by Circ 0001723

Biol Res. 2020 Aug 20;53(1):35. doi: 10.1186/s40659-020-00302-6.

Abstract

Background: Spinal cord injury (SCI) is a severe central nervous system trauma. The present study aimed to evaluate the effect of HIF-1α on inflammation in spinal cord injury (SCI) to uncover the molecular mechanisms of anti-inflammation.

Results: HIF-1α was reduced in SCI model rats and HIF-1α activation reduced TNF-α, IL-1β, IL-6 and IL-18 levels in SCI model rats. Meanwhile, Circ 0001723 expression was down-regulated and miR-380-3p expression was up-regulated in SCI model rats. In vitro model, down-regulation of Circ 0001723 promoted TNF-α, IL-1β, IL-6 and IL-18 levels, compared with control negative group. However, over-expression of Circ 0001723 reduced TNF-α, IL-1β, IL-6 and IL-18 levels in vitro model. Down-regulation of Circ 0001723 suppressed HIF-1α protein expressions and induced NLRP3 and Caspase-1 protein expressions in vitro model by up-regulation of miR-380-3p. Next, inactivation of HIF-1α reduced the pro-inflammation effects of Circ 0001723 in vitro model. Then, si-NLRP3 also inhibited the pro-inflammation effects of Circ 0001723 in vitro model via promotion of autophagy.

Conclusions: We concluded that HIF-1α reduced inflammation in spinal cord injury via miR-380-3p/ NLRP3 by Circ 0001723.

Keywords: Circ 0001723; HIF-1α; Inflammation; NLRP3; Spinal cord injury; miR-380-3p.

MeSH terms

  • Animals
  • Cytokines / blood
  • Gene Expression Regulation
  • Hypoxia-Inducible Factor 1, alpha Subunit / metabolism*
  • Inflammation / metabolism*
  • Male
  • MicroRNAs / genetics*
  • NLR Family, Pyrin Domain-Containing 3 Protein / metabolism*
  • RNA, Circular / genetics*
  • Rats
  • Rats, Sprague-Dawley
  • Spinal Cord Injuries / metabolism*

Substances

  • Cytokines
  • Hif1a protein, rat
  • Hypoxia-Inducible Factor 1, alpha Subunit
  • MicroRNAs
  • NLR Family, Pyrin Domain-Containing 3 Protein
  • Nlrp3 protein, rat
  • RNA, Circular