Work

FCGR1A Alleviates Ischemic Stroke-induced Injury by Promoting Anti-Inflammatory Microglial Polarization via the AMPK–mTOR Signaling Pathway

Year: 2025

Type: article

Abstract: Background: Ischemic stroke triggers inflammatory responses that lead to neuronal damage, with microglial polarization significantly influencing post-stroke inflammation. This study explores the role of Fc gamma receptor Ia (FCGR1A) in microglial polarization and its regulatory mechanisms in ischemic stroke. Methods: Differentially expressed genes (DEGs) associated with ischemic stroke were identified using the GSE58294 dataset. Hub genes were found by analyzing protein–protein interaction (PPI) networks. BV2 microglia were subjected to oxygen–glucose deprivation/reoxygenation (OGD/R) to mimic ischemic conditions in vitro, and FCGR1A and inflammatory marker levels were assessed. Besides, BV2 cells were stimulated with lipopolysaccharide (LPS) and interferon-gamma (IFN-γ) to induce M1 polarization, and the effects of FCGR1A overexpression and knockdown on cytokine production and microglial polarization were evaluated. The function of the AMP-activated protein kinase (AMPK)-mTOR pathway in regulating microglial polarization was further investigated using the mTOR inhibitor rapamycin (RAP). Results: From the 327 DEGs identified, FCGR1A was chosen as a hub gene. OGD/R treatment of BV2 cells produced a time-dependent rise in FCGR1A, induction of brown adipocytes 1 (Iba1), and interleukin 6 (IL-6) expression, indicating enhanced inflammation. FCGR1A overexpression induced a proinflammatory response and promoted M1 polarization, whereas FCGR1A knockdown reduced inflammation and shifted toward an anti-inflammatory M2 phenotype. Inhibition of the mTOR pathway using RAP, combined with FCGR1A knockdown, significantly enhanced AMPK activation and promoted a shift toward an anti-inflammatory M2 phenotype. Conclusion: FCGR1A modulates microglial polarization by affecting the AMPK–mTOR signaling pathway in ischemic conditions. Targeting FCGR1A and related pathways could offer new therapeutic strategies to lessen inflammation and facilitate the healing process after an ischemic stroke.

Source: Frontiers in Bioscience-Landmark

DOI: 10.31083/fbl26614