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

IF 4.4 3区医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Neurochemistry international Pub Date : 2023-11-01 DOI:10.1016/j.neuint.2023.105546

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

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引用次数: 0

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.

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体外氧-葡萄糖剥夺-再氧化后，排斥性引导分子a的敲低促进小胶质细胞极化进入抗炎表型。

排斥导向分子a（RGMa）是一种糖基磷脂酰肌醇锚定的糖蛋白，已被证明除了在大脑发育过程中调节神经元分化和存活外，还能影响神经炎症相关疾病。然而，RGMa在缺血性卒中后小胶质细胞极化中的任何功能或机制尚不清楚。在目前的研究中，发现RGMa在体外缺氧-葡萄糖剥夺-复氧（OGD/R）后在小胶质细胞中的表达水平降低。RGMa过表达诱导HAPI小胶质细胞主要极化为M1表型，促进促炎细胞因子的释放，敲低诱导M2表型，促进抗炎细胞因子的分泌。RGMa过表达还通过抑制过氧化物酶体增殖物激活受体γ（PPARγ）从细胞核向细胞质的转运来调节HAPI小胶质细胞的极化。RGMa的敲低产生了相反的作用，PPARγ拮抗剂GW9662逆转了这种作用。此外，RGMa敲低HAPI小胶质细胞条件培养基在体外提高了OGD/R后少突胶质细胞的存活率。因此，抑制RGMa可能是减少缺血性卒中后神经炎症的一种治疗策略。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Neurochemistry international 医学-神经科学

CiteScore

8.40

自引率

2.40%

发文量

128

审稿时长

37 days

期刊介绍： Neurochemistry International is devoted to the rapid publication of outstanding original articles and timely reviews in neurochemistry. Manuscripts on a broad range of topics will be considered, including molecular and cellular neurochemistry, neuropharmacology and genetic aspects of CNS function, neuroimmunology, metabolism as well as the neurochemistry of neurological and psychiatric disorders of the CNS.