脑血管周细胞表达钾离子通道Kir4.1在维持血流调控及脑缺血疾病的机制研究
批准号:
31970904
项目类别:
面上项目
资助金额:
58.0 万元
负责人:
童小萍
依托单位:
学科分类:
分子与细胞神经生物学
结题年份:
2023
批准年份:
2019
项目状态:
已结题
项目参与者:
童小萍
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中文摘要
Kir4.1主要被认为是大脑中胶质细胞特异性表达的一类内向整流钾离子通道,并对维持细胞静息膜电位、胞浆间隙的钾离子缓冲以及在各种脑疾病中都发挥着重要作用。我们最新的血管周细胞RNA测序分析发现血管周细胞高表达Kir4.1通道编码基因kcnj10。血管周细胞是神经血管单元和血脑屏障的重要细胞成分,与毛细血管内皮细胞紧密相连。先前研究普遍认为血管内皮细胞对血流调控起主要作用。周细胞包裹并贯穿全身的毛细血管和微静脉,在毛细血管壁上的覆盖率可达到32%。然而,周细胞在毛细血管对血流调控的作用却很少被研究报道。同时,对于周细胞表达kcnj10基因编码的Kir4.1通道的生物学功能目前更是知之甚少。本项目将系统解析血管周细胞表达Kir4.1离子通道对血流调控的分子、细胞学机制,并进一步深入理解血管周细胞表达Kir4.1通道在脑缺血疾病的病理发生机制,为临床治疗提供潜在的药物靶点和新思路。
英文摘要
Kir4.1 potassium channel is an inwardly rectified potassium channel specifically expressed in glial cells in the brain. Kir4.1 potassium channels are known to play an important role in maintaining cell resting membrane potentials, potassium buffering in extracellular space and in various brain diseases. In our latest genomic RNA sequencing data of neurovascular pericytes, we found that the Kir4.1 ion channel coding gene kcnj10 was highly expressed in these perivascular cells. Pericyte is one of important cell components of neurovascular unit and blood-brain barrier, which is closely connected with vascular endothelial cells. Previous studies have shown that endothelial cells play a major role in the regulation of blood flow. However, 90% of the brain capillaries are surrounded by pericytes and the coverage rate on the wall of capillaries by pericytes can reach to 32%, little is known how pericytes regulate capillary blood flow. At the meantime, the functional role of kcnj10 gene coded Kir4.1 channel expressed in pericytes has not been explored to date. The goal of this project aims to systematically study the molecular and cellular mechanisms of the capillary blood flow regulation by Kir4.1 potassium channel expressed in neurovascular pericytes, and to further understand the pathological mechanism of Kir4.1 channels in pericytes in brain ischemia disease. In all, we will illustrate the functional role and provide evidences of Kir4.1 channel expressed in pericytes as a potential clinical therapeutic target in vascular-related brain diseases.
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DOI:10.1038/s41467-021-25956-y.
发表时间:2021
期刊:Nature Communications
影响因子:16.6
作者:Zhang X;Liu Y;Hong X;Li X;Meshul C K;Moore C;Yang Y;Han Y;Li W;Xin Q;Lou H;Duan S;Xu T;Tong X
通讯作者:Tong X
DOI:10.1038/s41380-020-00930-0.
发表时间:2021
期刊:Molecular Psychiatry
影响因子:--
作者:Zhou B;Zhu Z;Ransom B R;Tong X
通讯作者:Tong X
Kir4.1 channel activation in NG2 glia contributes to remyelination in ischemic stroke.
NG2 神经胶质细胞中的 Kir4.1 通道激活有助于缺血性中风的髓鞘再生。
DOI:10.1016/j.ebiom.2022.104406
发表时间:2023-01
期刊:EBIOMEDICINE
影响因子:11.1
作者:Hong, Xiaoqi;Jian, Yujin;Ding, Shenghao;Zhou, Jianpo;Zheng, Xiaoli;Zhang, Huimin;Zhou, Butian;Zhuang, Canbin;Wan, Jieqing;Tong, Xiaoping
通讯作者:Tong, Xiaoping
DOI:10.1002/glia.
发表时间:2021
期刊:Glia
影响因子:--
作者:Zhang H;Zhang X;Hong X;Tong X
通讯作者:Tong X
DOI:10.1002/glia.24343
发表时间:2023
期刊:Glia
影响因子:--
作者:Liu Y;Shen X;Zhang Y;Zheng X;Cepeda C;Wang Y;Duan S;Tong X
通讯作者:Tong X
少突胶质谱系细胞Kir4.1离子通道介导多发性硬化症的病理机制研究
- 批准号:--
- 项目类别:面上项目
- 资助金额:51万元
- 批准年份:2022
- 负责人:童小萍
- 依托单位:
NG2胶质细胞参与海马区学习、记忆功能调控的神经环路基础
- 批准号:91632104
- 项目类别:重大研究计划
- 资助金额:60.0万元
- 批准年份:2016
- 负责人:童小萍
- 依托单位:
NG2胶质细胞对海马区神经环路调控的机制研究
- 批准号:31571063
- 项目类别:面上项目
- 资助金额:64.0万元
- 批准年份:2015
- 负责人:童小萍
- 依托单位:
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