PRMT8 通过调节小胶质细胞的激活和极化来减轻脑缺血/再灌注损伤，从而通过上调 Lin28a 来抑制神经炎症,ACS Chemical Neuroscience

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PRMT8 通过调节小胶质细胞的激活和极化来减轻脑缺血/再灌注损伤，从而通过上调 Lin28a 来抑制神经炎症
ACS Chemical Neuroscience ( IF 4.1 ) Pub Date : 2022-03-11 , DOI: 10.1021/acschemneuro.2c00096
Kuang Zheng ₁ , Yuliang Zhang ₁ , Chengwei Zhang ₁ , Wangyang Ye ₁ , Chenxing Ye ₁ , Xianxi Tan ₁ , Ye Xiong ₁

Affiliation

小胶质细胞的激活和极化参与神经炎症并调节缺血性中风相关的脑损伤。蛋白质精氨酸甲基转移酶 8 作为缺氧应激诱导的神经炎症的调节成分起作用。研究了蛋白质精氨酸甲基转移酶 8 (PRMT8) 通过调节小胶质细胞活化和极化对缺血性中风相关脑损伤的保护作用。首先，PRMT8 在大脑中动脉闭塞 (MCAO) 诱导的小鼠和氧 - 葡萄糖剥夺/复氧 (OGD/R) 诱导的 SH-SY5Y 中下调。注射 AAV-PRMT8 可减少 MCAO 诱导的小鼠的梗塞体积。此外，注射 AAV-PRMT8 可促进神经元存活并改善 MCAO 诱导小鼠大脑的组织病理学变化。注射 AAV-PRMT8 可抑制 MCAO 诱导小鼠的神经元凋亡和神经炎症。其次，PRMT8 过表达增加细胞活力并抑制 OGD/R 诱导的 SH-SY5Y 的细胞凋亡和炎症。第三，注射 AAV-PRMT8 减少了近 50% 的 CD86 + M1 小胶质细胞，增强了约 20% 的 CD206 + M2 小胶质细胞。此外，PRMT8 过表达减弱了 OGD/R 诱导的 BV2 的 M1 表型极化。最后，PRMT8 上调 Lin28a 和 Lin28a 的缺失减弱了 PRMT8 过表达诱导的细胞活力增加和 OGD/R 诱导的 SH-SY5Y 的细胞凋亡和炎症减少。总之，PRMT8通过上调Lin28a促进小胶质细胞的M2表型极化并抑制神经元凋亡以改善脑缺血/再灌注损伤。

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PRMT8 Attenuates Cerebral Ischemia/Reperfusion Injury via Modulating Microglia Activation and Polarization to Suppress Neuroinflammation by Upregulating Lin28a

Activation and polarization of microglia are involved in neuroinflammation and regulate ischemic stroke-associated brain injury. Protein arginine methyltransferase 8 functions as a regulatory component of hypoxic stress-induced neuroinflammation. The protective effect of protein arginine methyltransferase 8 (PRMT8) against ischemic stroke-associated brain injury through regulation of microglia activation and polarization was investigated. First, PRMT8 was downregulated in middle cerebral artery occlusion (MCAO)-induced mice and oxygen–glucose deprivation/reoxygenation (OGD/R)-induced SH-SY5Y. Injection with AAV-PRMT8 reduced infarct volumes in MCAO-induced mice. Moreover, injection with AAV-PRMT8 promoted neuronal survival and ameliorated histopathological changes in the brains of MCAO-induced mice. The neuronal apoptosis and neuroinflammation in MCAO-induced mice were suppressed by AAV-PRMT8 injection. Second, PRMT8 overexpression increased cell viability and suppressed the cell apoptosis and inflammation of OGD/R-induced SH-SY5Y. Third, injection with AAV-PRMT8 reduced almost 50% of CD86 + M1 microglia and enhanced about 20% of CD206 + M2 microglia. Furthermore, PRMT8 overexpression attenuated OGD/R-induced M1 phenotype polarization of BV2. Lastly, PRMT8 upregulated Lin28a and loss of Lin28a attenuated PRMT8 overexpression-induced increase in cell viability and decrease in cell apoptosis and inflammation of OGD/R-induced SH-SY5Y. In conclusion, PRMT8 promoted M2 phenotype polarization of microglia and suppressed neuronal apoptosis to ameliorate cerebral ischemia/reperfusion injury through upregulation of Lin28a.

更新日期：2022-03-11

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