Exploring the Role of Microglia Activation in Ischemia Stroke Based on the circDnajc1/miR-27a-5p/C1qc Signaling Axis

Shuangping Li1,2, Qingping Ye1,2, Yumeng Li1,2

  • 1Department of Pharmacy, The First Affiliated Hospital of Anhui University of Chinese Medicine, No 117 Meishan Road, Shushan District, Hefei, 230031, China.

Insights

This study reveals circular RNA circDnajc1 promotes ischemia stroke by activating microglia and increasing inflammation. Targeting circDnajc1 offers a potential therapeutic strategy for stroke.

Area of Science:

  • Neuroscience
  • Molecular Biology
  • Genetics

Background:

  • Ischemia stroke, induced by middle cerebral artery occlusion/reperfusion (MCAO/R), is a significant health concern with incompletely understood molecular mechanisms.
  • Circular RNAs (circRNAs) are emerging as critical regulators in various biological processes, but their role in MCAO/R-induced ischemia stroke is largely unexplored.

Purpose of the Study:

  • To investigate the role and underlying mechanisms of the circDnajc1/miR-27a-5p/C1qc signaling pathway in the development of ischemia stroke.
  • To elucidate how circDnajc1 influences microglial activation, inflammatory responses, and neuronal apoptosis in the context of stroke.

Main Methods:

  • Established in vitro (oxygen-glucose deprivation/reperfusion in co-cultured neurons and microglia) and in vivo (MCAO/R rat model) ischemia stroke models.
  • Utilized techniques including siRNA/overexpression vectors for circDnajc1 manipulation, flow cytometry, RT-qPCR, immunofluorescence, RNA immunoprecipitation, and luciferase reporter assays to explore molecular mechanisms.

Main Results:

  • In vitro, circDnajc1 promoted microglial activation, inflammatory factor release, downregulated miR-27a-5p, and upregulated C1qc, C3, and C5ar, leading to neuronal apoptosis.
  • In vivo, circDnajc1 knockdown protected neurons in MCAO/R rats, inhibited microglial activation, and reduced inflammatory factor release.
  • CircDnajc1 was confirmed to regulate the expression of miR-27a-5p's downstream targets, including C1qc, C3, and C5ar.

Conclusions:

  • CircDnajc1 plays a critical role in ischemia stroke pathogenesis.
  • The circDnajc1/miR-27a-5p/C1qc signaling axis is a key pathway influencing nervous system homeostasis by modulating microglial activation, inflammation, and neuronal apoptosis.
  • CircDnajc1 represents a potential therapeutic target for treating ischemia stroke.