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

• Published in: Cell death and differentiation Vol. 25; no. 10; pp. 1870 - 1884
• Main Authors: 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
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01.10.2018; Nature Publishing Group
• Subjects: 13/106; 13/109; 13/51; 13/89; 14/19; 38/77; 631/80/79/2028; 692/699/375; 82/1; 82/29; 82/80; Adaptor Proteins, Signal Transducing - chemistry; Adaptor Proteins, Signal Transducing - metabolism; Animals; Apoptosis; Astrocytes; Astrocytes - cytology; Astrocytes - drug effects; Astrocytes - metabolism; Biochemistry; Biomedical and Life Sciences; Cell Biology; Cell Cycle Analysis; Cell Cycle Proteins; Cell Nucleus - metabolism; Cell Proliferation; Cells, Cultured; Central nervous system; Cerebral Hemorrhage - metabolism; Cerebral Hemorrhage - pathology; Connexin 43; Connexin 43 - antagonists & inhibitors; Connexin 43 - genetics; Connexin 43 - metabolism; Down-Regulation - drug effects; Epithelial-Mesenchymal Transition - drug effects; Glial fibrillary acidic protein; Glial Fibrillary Acidic Protein - metabolism; Gliosis; Hemoglobin; Hemoglobins - pharmacology; Hemorrhage; Immunofluorescence; Immunoprecipitation; Interleukin-1beta - genetics; Interleukin-1beta - metabolism; Life Sciences; Mesenchyme; Mice; Microscopy, Fluorescence; Nuclear transport; Phosphoproteins - chemistry; Phosphoproteins - metabolism; Protein Binding; Protein Transport - drug effects; RNA Interference; RNA, Small Interfering - metabolism; siRNA; Stem Cells; Therapeutic applications; Vimentin; Yes-associated protein
• ISSN: 1350-9047; 1476-5403; 1476-5403
• DOI: 10.1038/s41418-018-0137-0

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.