A connexin43/YAP axis regulates astroglial-mesenchymal transition in hemoglobin induced astrocyte activation.
A connexin43/YAP axis regulates astroglial-mesenchymal transition in hemoglobin induced astrocyte activation.
复制标题
connexin43/YAP 轴调节血红蛋白诱导的星形胶质细胞激活中的星形胶质细胞-间质转化。
DOI：
10.1038/s41418-018-0137-0
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发表时间：
2018
影响因子：
12.4
通讯作者：
Bian Liuguan
中科院分区：
文献类型：
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作者：
Yang Yong;Ren Jie;Sun Yuhao;Xue Yuan;Zhang Zhijian;Gong Aihua;Wang Baofeng;Zhong Zhihong;Cui Zhenwen;Xi Zhiyu;Yang Guo-Yuan;Sun Qingfang;Bian Liuguan
反应性星形胶质细胞增多症是中枢神经系统受到侮辱时的常见反应，但其机制尚不清楚。在本研究中，我们发现胶质纤维酸性蛋白(GFAP)和Vimentin在脑出血(ICH)小鼠脑内的时空差异表达，提示星形胶质细胞的去分化和星形胶质细胞-间充质转化(AMT)可能是反应性星形胶质细胞增生症的早期事件。进一步，我们验证了在暴露于血红蛋白(Hb)的纯化星形胶质细胞培养中AMT的发现。此外，在Hb激活的星形胶质细胞中还观察到连接蛋白43(Cx43)的下调和YAP核转位。SiRNA敲除Cx43后引发YAP核转位。通过免疫荧光和免疫共沉淀确定Cx43和YAP在物理上是相关联的。我们认为，星形胶质细胞在Hb诱导的激活过程中经历AMT，而Cx43下调促进YAP核转位是参与这一过程的一种新机制。Cx43-YAP相互作用可能是调控星形胶质细胞激活的潜在治疗靶点。
Reactive astrogliosis is a common response to insults to the central nervous system, but the mechanism remains unknown. In this study, we found the temporal and spatial differential expression of glial fibrillary acidic protein (GFAP) and Vimentin in the intracerebral hemorrhage (ICH) mouse brain, indicating that the de-differentiation and astroglial-mesenchymal transition (AMT) of astrocytes might be an early event in reactive astrogliosis. Further we verified the AMT finding in purified astrocyte cultures exposed to hemoglobin (Hb). Additionally, Connexin 43 (Cx43) downregulation and YAP nuclear translocation were observed in Hb-activated astrocytes. Knocking down Cx43 by siRNA triggered YAP nuclear translocation. Cx43 and YAP were physically associated as determined by immunofluorescence and co-immunoprecipitation. We propose that astrocytes undergo AMT during Hb-induced activation where Cx43 downregulation facilitates YAP nuclear translocation is a novel mechanism involved in this process. Cx43-YAP interaction may represent a potential therapeutic target for modulating astrocyte activation.