Knockdown of repulsive guidance molecule a promotes polarization of microglia into an anti-inflammatory phenotype after oxygen-glucose deprivation-reoxygenation<i> in</i><i> vitro</i>

作者全名："Shen, Guanru; Xiao, Hongmei; Huang, Siyuan; Yuan, Xiaofan; Rongrong, Zhang; Ma, Yue; Qin, Xinyue"

作者地址："[Shen, Guanru; Xiao, Hongmei; Huang, Siyuan; Yuan, Xiaofan; Rongrong, Zhang; Ma, Yue; Qin, Xinyue] Chongqing Med Univ, Affiliated Hosp 1, Dept Neurol, Chongqing 400016, Peoples R China; [Qin, Xinyue] 1 Youyi Rd, Chongqing, Peoples R China"

通信作者："Qin, XY (通讯作者)，1 Youyi Rd, Chongqing, Peoples R China."

来源：NEUROCHEMISTRY INTERNATIONAL

ESI学科分类：NEUROSCIENCE & BEHAVIOR

WOS号：WOS:001076010000001

JCR分区：Q1

影响因子：4.4

年份：2023

卷号：170

期号：　

开始页：　

结束页：　

文献类型：Article

关键词：RGMa; Ischemic stroke; Microglia; Oligodendrocyte; PPAR gamma

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 over-expression 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 gamma (PPAR gamma) from the nucleus to cytoplasm. The opposite effect resulted from RGMa-knockdown and was reversed by the PPAR gamma 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."

基金机构：National Natural Science Foundation of China [81771275]

基金资助正文：This study is supported by the National Natural Science Foundation of China (81771275) .