A connexin43/YAP axis regulates astroglial-mesenchymal transition in hemoglobin induced astrocyte activation

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^*

来源：Cell Death and Differentiation, 2018, 25(10): 1870-1884.

DOI：10.1038/s41418-018-0137-0

• HIPPO PATHWAY
• RADIAL GLIA
• CELL-PROLIFERATION
• CONTACT INHIBITION
• MOUSE MODEL
• STEM-CELLS
• YAP
• CONNEXIN-43
• TISSUE
• BRAIN

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 coimmunoprecipitation. 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.

• 出版日期2018-10
• 单位广东省人民医院; 青岛大学; 江苏大学; 镇江市疾病预防控制中心; 上海市闵行区中心医院; 上海交通大学