{"title":"FCGR1A通过AMPK-mTOR信号通路促进抗炎小胶质细胞极化，减轻缺血性卒中损伤。","authors":"Meng Liu, Xuhui Fan, Dongya Chen, Huibin Yao, Zhihui Huang, Heng Li, Qing Zhang, Yuqi Wang, Haihan Song, Yufeng Yan","doi":"10.31083/FBL26614","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>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 (<i>FCGR1A</i>) in microglial polarization and its regulatory mechanisms in ischemic stroke.</p><p><strong>Methods: </strong>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 <i>in vitro</i>, and <i>FCGR1A</i> 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 <i>FCGR1A</i> 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).</p><p><strong>Results: </strong>From the 327 DEGs identified, <i>FCGR1A</i> 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. <i>FCGR1A</i> overexpression induced a proinflammatory response and promoted M1 polarization, whereas <i>FCGR1A</i> knockdown reduced inflammation and shifted toward an anti-inflammatory M2 phenotype. Inhibition of the mTOR pathway using RAP, combined with <i>FCGR1A</i> knockdown, significantly enhanced AMPK activation and promoted a shift toward an anti-inflammatory M2 phenotype.</p><p><strong>Conclusion: </strong><i>FCGR1A</i> modulates microglial polarization by affecting the AMPK-mTOR signaling pathway in ischemic conditions. Targeting <i>FCGR1A</i> and related pathways could offer new therapeutic strategies to lessen inflammation and facilitate the healing process after an ischemic stroke.</p>","PeriodicalId":73069,"journal":{"name":"Frontiers in bioscience (Landmark edition)","volume":"30 5","pages":"26614"},"PeriodicalIF":3.3000,"publicationDate":"2025-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"FCGR1A Alleviates Ischemic Stroke-induced Injury by Promoting Anti-Inflammatory Microglial Polarization via the AMPK-mTOR Signaling Pathway.\",\"authors\":\"Meng Liu, Xuhui Fan, Dongya Chen, Huibin Yao, Zhihui Huang, Heng Li, Qing Zhang, Yuqi Wang, Haihan Song, Yufeng Yan\",\"doi\":\"10.31083/FBL26614\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>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 (<i>FCGR1A</i>) in microglial polarization and its regulatory mechanisms in ischemic stroke.</p><p><strong>Methods: </strong>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 <i>in vitro</i>, and <i>FCGR1A</i> 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 <i>FCGR1A</i> 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).</p><p><strong>Results: </strong>From the 327 DEGs identified, <i>FCGR1A</i> 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. <i>FCGR1A</i> overexpression induced a proinflammatory response and promoted M1 polarization, whereas <i>FCGR1A</i> knockdown reduced inflammation and shifted toward an anti-inflammatory M2 phenotype. Inhibition of the mTOR pathway using RAP, combined with <i>FCGR1A</i> knockdown, significantly enhanced AMPK activation and promoted a shift toward an anti-inflammatory M2 phenotype.</p><p><strong>Conclusion: </strong><i>FCGR1A</i> modulates microglial polarization by affecting the AMPK-mTOR signaling pathway in ischemic conditions. Targeting <i>FCGR1A</i> and related pathways could offer new therapeutic strategies to lessen inflammation and facilitate the healing process after an ischemic stroke.</p>\",\"PeriodicalId\":73069,\"journal\":{\"name\":\"Frontiers in bioscience (Landmark edition)\",\"volume\":\"30 5\",\"pages\":\"26614\"},\"PeriodicalIF\":3.3000,\"publicationDate\":\"2025-04-29\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Frontiers in bioscience (Landmark edition)\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://doi.org/10.31083/FBL26614\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"BIOCHEMISTRY & MOLECULAR BIOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Frontiers in bioscience (Landmark edition)","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.31083/FBL26614","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"BIOCHEMISTRY & MOLECULAR BIOLOGY","Score":null,"Total":0}
FCGR1A Alleviates Ischemic Stroke-induced Injury by Promoting Anti-Inflammatory Microglial Polarization via the AMPK-mTOR Signaling Pathway.
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.
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