小窝蛋白1
髓鞘
KLF2
基因敲除
缺血
细胞生物学
热休克蛋白
平衡
少突胶质细胞
生物
血管内皮生长因子B
神经科学
医学
内科学
癌症研究
下调和上调
中枢神经系统
血管内皮生长因子A
血管内皮生长因子
细胞培养
遗传学
基因
血管内皮生长因子受体
作者
Ying Zhao,Wusheng Zhu,Ting Wan,Xiaohao Zhang,Yunzi Li,Zhenqian Huang,Pengfei Xu,Kangmo Huang,Ruidong Ye,Yi Xie,Xinfeng Liu
标识
DOI:10.1038/s41467-022-34293-7
摘要
Oligovascular coupling contributes to white matter vascular homeostasis. However, little is known about the effects of oligovascular interaction on oligodendrocyte precursor cell (OPC) changes in chronic cerebral ischemia. Here, using a mouse of bilateral carotid artery stenosis, we show a gradual accumulation of OPCs on vasculature with impaired oligodendrogenesis. Mechanistically, chronic ischemia induces a substantial loss of endothelial caveolin-1 (Cav-1), leading to vascular secretion of heat shock protein 90α (HSP90α). Endothelial-specific over-expression of Cav-1 or genetic knockdown of vascular HSP90α restores normal vascular-OPC interaction, promotes oligodendrogenesis and attenuates ischemic myelin damage. miR-3074(-1)-3p is identified as a direct inducer of Cav-1 reduction in mice and humans. Endothelial uptake of nanoparticle-antagomir improves myelin damage and cognitive deficits dependent on Cav-1. In summary, our findings demonstrate that vascular abnormality may compromise oligodendrogenesis and myelin regeneration through endothelial Cav-1, which may provide an intercellular mechanism in ischemic demyelination.
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