基因敲除
小胶质细胞
神经炎症
促炎细胞因子
细胞生物学
生物
内分泌学
内科学
化学
炎症
免疫学
医学
生物化学
细胞凋亡
作者
Guanru Shen,Hongmei Xiao,Siyuan Huang,Xiaofan Yuan,Rongrong Zhang,Yue Ma,Xinyue Qin
标识
DOI:10.1016/j.neuint.2023.105546
摘要
Repulsive guidance molecule a (RGMa) is a glycosylphosphatidylinositol-anchored glycoprotein that has been demonstrated to influence neuroinflammatory-related diseases in addition to regulating neuronal differentiation and survival during brain development. However, any function or mechanism of RGMa in the polarization of microglia after ischemic stroke remains unclear. In the current study, RGMa was found to be expressed at reduced levels in microglia after oxygen-glucose deprivation-reoxygenation (OGD/R) in vitro. RGMa overexpression induced HAPI microglia to predominantly polarize to the M1 phenotype, promoting the release of proinflammatory cytokines and knockdown induced the M2 phenotype, promoting the release of anti-inflammatory cytokines. RGMa overexpression also regulated the polarization of HAPI microglia by inhibiting the transportation of peroxisome proliferator-activated receptor γ (PPARγ) from the nucleus to cytoplasm. The opposite effect resulted from RGMa-knockdown and was reversed by the PPARγ antagonist, GW9662. In addition, RGMa-knockdown HAPI microglial conditioned medium improved the survival of oligodendrocytes after OGD/R in vitro. Thus, inhibition of RGMa may constitute a therapeutic strategy for reducing neuroinflammation after ischemic stroke.
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