Macrophage Nuclear Receptor Corepressor 1 Deficiency Protects Against Ischemic Stroke in Mice
Macrophage Nuclear Receptor Corepressor 1 Deficiency Protects Against Ischemic Stroke in Mice
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巨噬细胞核受体辅阻遏物 1 缺陷可预防小鼠缺血性中风
DOI：
10.1007/s12265-021-10187-9
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发表时间：
2022-01
影响因子：
3.4
通讯作者：
Sheng-Zhong Duan
中科院分区：
文献类型：
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作者：
Shuai Shao;Yan-Lin Chen;Lin Juan Du;Hong Zhu;Lu Jun Zhou;Ting Liu;Wen-Zhen Lin;Fei Yu;Xiao-Xin Ma;Xue Rui Shi;Xiao-Qian Meng;Yuan Liu;Yongting Wang;Lan Bai;Xue‐Qing Zhang;Feng Jia;Sheng-Zhong Duan
小胶质细胞/巨噬细胞活化在缺血性卒中(IS)中起重要作用。核受体辅阻遏子1(NCoR1)是巨噬细胞的重要调节因子。本研究旨在探讨巨噬细胞NCoR1在IS中的作用。巨噬细胞NCoR1基因敲除(MNKO)小鼠和仔鼠对照组小鼠采用大脑中动脉阻塞(MCAO)模型。我们的数据显示，巨噬细胞NCoR1缺乏显著减少了MCAO后的脑梗塞面积和梗塞体积以及脑水肿。此外，MNKO还可减少脑缺血后小胶质细胞/巨噬细胞的浸润和活化、神经炎症、神经元细胞的凋亡和血脑屏障的破坏。机制研究表明，Ncor1与LxRβ在小胶质细胞内相互作用，MNKO损害IS后脑组织核因子-κB信号通路的激活。我们的数据表明，巨噬细胞NCoR1缺乏抑制了小胶质细胞/巨噬细胞的激活，并对IS具有保护作用。在小胶质细胞/巨噬细胞中靶向NCoR1可能是治疗IS的一种潜在方法。
Microglia/macrophage activation plays an essential role in Ischemic stroke (IS). Nuclear receptor corepressor 1 (NCoR1) has been identified as a vital regulator in macrophages. The present study aims to explore the functions of macrophage NCoR1 in IS. Macrophage NCoR1 knockout (MNKO) mice and littermate control mice were subjected to middle cerebral artery occlusion (MCAO). Our data showed that macrophage NCoR1 deficiency significantly reduced the infarct size and infarct volume as well as brain edema after MCAO. Additionally, MNKO induced less microglia/macrophage infiltration and activation, neuroinflammation, apoptosis of neuronal cells, and BBB disruption in brains after IS. Mechanistic studies revealed that NCoR1 interacted with LXRβ in microglia and MNKO impaired the activation of the Nuclear factor-κB signaling pathway in brains after IS. Our data demonstrated that macrophage NCoR1 deficiency inhibited microglia/macrophage activation and protected against IS. Targeting NCoR1 in microglia/macrophage may be a potential approach for IS treatment.
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影响因子：
15.1
作者：
Cui J;Chen S;Zhang C;Meng F;Wu W;Hu R;Hadass O;Lehmidi T;Blair GJ;Lee M;Chang M;Mobashery S;Sun GY;Gu Z
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影响因子：
5.5
作者：
Liu, Zong-Jian;Ran, Yuan-Yuan;Xi, Jia-Ning
通讯作者：
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影响因子：
14.5
作者：
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通讯作者：
Lee, Sung Joong
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影响因子：
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作者：
Lu, Yifei;Li, Chao;Jiang, Chen
通讯作者：
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