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

Guanru Shen; Hongmei Xiao; Siyuan Huang; Xiaofan Yuan; Zhang Rongrong; Yue Ma; Xinyue Qin

doi:10.1016/j.neuint.2023.105546

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

Neurochem Int. 2023 Nov:170:105546. doi: 10.1016/j.neuint.2023.105546. Epub 2023 May 9.

Authors

Guanru Shen¹, Hongmei Xiao¹, Siyuan Huang¹, Xiaofan Yuan¹, Zhang Rongrong¹, Yue Ma¹, Xinyue Qin²

Affiliations

¹ Department of Neurology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, China.
² Department of Neurology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, China. Electronic address: qinxy20021@sina.com.

PMID: 37169181
DOI: 10.1016/j.neuint.2023.105546

Abstract

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.

Keywords: Ischemic stroke; Microglia; Oligodendrocyte; PPARγ; RGMa.