Up-regulating lncRNA OIP5-AS1 protects neuron injury against cerebral hypoxia-ischemia induced inflammation and oxidative stress in microglia/macrophage through activating CTRP3 via sponging miR-186-5p

Int Immunopharmacol. 2021 Mar:92:107339. doi: 10.1016/j.intimp.2020.107339. Epub 2021 Jan 27.

Abstract

Background: Inflammation and oxidative stress is closely associated with the development of ischemic brain stroke. Opa-interacting protein 5 antisense RNA 1 (OIP5-AS1), a novel identified long non-coding RNA (lncRNA), has been suggested to play an important role in the development of many types of human cancers. However, the functional involvement of OIP5-AS1 in ischemic stroke is still unknown.

Methods: Quantitative real-time polymerase chain reaction and /or western blot were conducted to determine the expression profiles of OIP5-AS1, C1q/TNF-related protein 3 (CTRP3) and miR-186-5p in the serum of stroke patients, as well as in the ischemic penumbra of rats with middle cerebral artery occlusion/reperfusion (MCAO/R) injury and microglial cells treated with oxygen glucose deprivation/re-oxygenation (OGD/R). Upon selective regulation of OIP5-AS1 and miR-186-5p, the inflammation and oxidative stress responses in microglia/macrophage as well as neurologic functions in MCAO/R rats were detected. Furthermore, the interactions between OIP5-AS1 and miR-186-5p, miR-186-5p and CTRP3 were investigated by RNA immunoprecipitation (RIP) assay, luciferase report assay and bioinformation anaylsis.

Results: We observed markedly increased infarct volume, neuronal apoptosis, inflammation and oxidative stress responses in the infarcted lesions of MCAO/R rats, in line with down-regulated levels of OIP5-AS1 and CTRP3 while up-regulated miR-186-5p. Functional studies demonstrated that up-regulation of OIP5-AS1 attenuated infarct volume, neuronal apoptosis, microglia/macrophage inflammation and oxidative stress responses induced by MCAO/R or OGD/R. In terms of mechanism, we revealed that OIP5-AS1-miR-186-5p-CTRP3 axis played a vital role in modulating microglia/macrophage activation and neuronal apoptosis.

Conclusion: Up-regulating lncRNA OIP5-AS1 protects neuron injury against MCAO/R induced inflammation and oxidative stress in microglia/macrophage through activating CTRP3 via sponging miR-186-5p.

Keywords: Cerebral hypoxia-ischemia; Inflammation; Microglia; OIP5-AS1; miR-186-5p.

MeSH terms

  • Animals
  • Cells, Cultured
  • Disease Models, Animal
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Hypoxia-Ischemia, Brain / complications*
  • Inflammation / etiology
  • Inflammation / metabolism
  • Inflammation / pathology
  • Inflammation / prevention & control*
  • Macrophages / metabolism
  • Macrophages / pathology
  • Mice
  • MicroRNAs / genetics*
  • Microglia / metabolism
  • Microglia / pathology
  • Neurons / metabolism*
  • Neurons / pathology
  • Oxidative Stress*
  • RNA, Long Noncoding / genetics*
  • Rats
  • Signal Transduction
  • Stroke / etiology
  • Stroke / metabolism
  • Stroke / pathology
  • Stroke / prevention & control
  • Tumor Necrosis Factors / metabolism*

Substances

  • C1QTNF3 protein, human
  • MIRN186 microRNA, human
  • MicroRNAs
  • RNA, Long Noncoding
  • Tumor Necrosis Factors
  • long noncoding RNA OIP5, human