microRNA-367-3p regulation of GPRC5A is suppressed in ischemic stroke

J Cereb Blood Flow Metab. 2020 Jun;40(6):1300-1315. doi: 10.1177/0271678X19858637. Epub 2019 Jul 11.

Abstract

Ischemic stroke is a major cause of mortality and long-term disability with limited treatment options, and a greater understanding of the gene regulatory mechanisms underlying ischemic stroke-associated neuroinflammation is required for new therapies. To study ischemic stroke in vivo, mice were subjected to sustained ischemia by intraluminal filament-induced middle cerebral artery occlusion (MCAo) for 24 h without reperfusion or transient ischemia for 30 min followed by 23.5 h reperfusion, and brain miRNA and mRNA expression changes were quantified by TaqMan OpenArrays and gene (mRNA) expression arrays, respectively. Sustained ischemia resulted in 18 significantly altered miRNAs and 392 altered mRNAs in mouse brains compared to Sham controls; however, the transient ischemic condition was found to impact only 6 miRNAs and 126 mRNAs. miR-367-3p was found to be significantly decreased in brain homogenates with sustained ischemia. G protein-coupled receptor, family C, group 5, member A (Gprc5a), a miR-367-3p target gene, was found to be significantly increased with sustained ischemia. In primary neurons, inhibition of endogenous miR-367-3p resulted in a significant increase in Gprc5a expression. Moreover, miR-367-3p was found to be co-expressed with GPRC5A in human neurons. Results suggest that loss of miR-367-3p suppression of GPRC5A may contribute to neuroinflammation associated with ischemic stroke.

Keywords: Microrna; brain; ischemia; neuroinflammation; neurons; stroke.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Gene Expression Regulation / physiology*
  • Inflammation / metabolism
  • Ischemic Stroke / metabolism*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • MicroRNAs / metabolism*
  • Receptors, G-Protein-Coupled / biosynthesis*

Substances

  • GPRC5A protein, mouse
  • MIRN367 microRNA, mouse
  • MicroRNAs
  • Receptors, G-Protein-Coupled