LncRNA FIRRE/NF-kB feedback loop contributes to OGD/R injury of cerebral microglial cells

Biochem Biophys Res Commun. 2018 Jun 18;501(1):131-138. doi: 10.1016/j.bbrc.2018.04.194. Epub 2018 May 8.

Abstract

Stroke is one of the leading causes for serious long-term neurological disability. LncRNAs have been investigated to be dysregulated in ischemic stroke. However, the underlying mechanisms of some specific lncRNAs have not been clearly clarified. To determine lncRNA-mediated regulatory mechanism in ischemic stroke, we constructed OGD/R injury model of cerebral microglial cells. Microarray analysis was carried out and analyzed that lncRNA functional intergenic repeating RNA element (FIRRE) was associated with OGD/R injury. Based on the molecular biotechnology, we demonstrated that FIRRE could activate NF-kB signal pathway. Meanwhile, the activated NF-kB promoted FIRRE expression in OGD/R-treated cerebral microglial cells. Therefore, FIRRE and NF-kB formed a positive feedback loop to promote the transcription of NLRP3 inflammasome, thus contributed to the OGD/R injury of cerebral microglial cells. All findings in this study may help to explore novel and specific therapeutic target for ischemic stroke.

Keywords: FIRRE; NF-kB; NLRP3; Stroke.

MeSH terms

  • Animals
  • Cells, Cultured
  • Cerebrum / injuries
  • Cerebrum / metabolism*
  • Cerebrum / pathology*
  • Feedback, Physiological
  • Glucose / metabolism
  • Inflammasomes / metabolism
  • Microglia / metabolism*
  • Microglia / pathology*
  • Models, Neurological
  • NF-kappa B / metabolism*
  • NLR Family, Pyrin Domain-Containing 3 Protein / genetics
  • NLR Family, Pyrin Domain-Containing 3 Protein / metabolism
  • Oxygen / metabolism
  • RNA, Long Noncoding / genetics*
  • RNA, Long Noncoding / metabolism*
  • Rats
  • Up-Regulation

Substances

  • Inflammasomes
  • NF-kappa B
  • NLR Family, Pyrin Domain-Containing 3 Protein
  • Nlrp3 protein, rat
  • RNA, Long Noncoding
  • Glucose
  • Oxygen