title: YAP Is a Critical Inducer of SOCS3, Preventing Reactive Astrogliosis.
abstract: Yes-associated protein (YAP) is a key transcriptional cofactor of the Hippo pathway, critical for the development of multiple organs. However, its role in the developing brain remains poorly understood. Here, we found that YAP was highly expressed in astrocytes and YAP deletion elevated the astrocytic activation in culture and in vivo, which was associated with microglial activation. At the molecular level, YAP in astrocytes was activated by IFNβ or ciliary neurotrophic factor (CNTF), which was necessary for IFNβ or CNTF induction of the suppressor of cytokine signaling 3 (SOCS3), a negative regulator of the Janus kinase-signal transducer and activator of transcription (JAK-STAT) inflammatory pathway. YAP(-/-) astrocytes thus showed hyperactivation of the JAK-STAT inflammatory pathway and reactive astrogliosis. Expression of SOCS3 in YAP(-/-) astrocytes prevented the hyperactivation of STAT3 and partially restored the astrocytic activation. Finally, reactive astrogliosis was associated with blood-brain barrier dysfunction in YAP brain-selective knockout mice. Taken together, these results identify unrecognized functions of YAP in preventing reactive astrogliosis and reveal a pathway of YAP-SOCS for the negatively control of neuroinflammation.
authors.affiliation: Department of Neuroscience and Regenerative Medicine and Department of Neurology.|Charlie Norwood VA Medical Center, Augusta, GA 30912, USA.|Institute of Hypoxia Medicine and Institute of Neuroscience, Wenzhou Medical University, Wenzhou, Zhejiang 325035, China.
authors.forename: Zhihui
authors.initials: Z
authors.lastname: Huang
authors.affiliation: Department of Neuroscience and Regenerative Medicine and Department of Neurology.|Charlie Norwood VA Medical Center, Augusta, GA 30912, USA.|Research Center of Blood Transfusion Medicine, Key Laboratory of Laboratory Medicine (Wenzhou Medical University), Ministry of Education, Zhejiang Provincial People's Hospital, Hangzhou, Zhejiang 310014, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Pharmacology and Toxicology, Medical College of Georgia, Georgia Regents University, Augusta, GA 30912, USA.
authors.forename: Guoqing
authors.initials: G
authors.lastname: Hu
authors.affiliation: Department of Pharmacology and Toxicology, Medical College of Georgia, Georgia Regents University, Augusta, GA 30912, USA.
authors.forename: Jiliang
authors.initials: J
authors.lastname: Zhou
authors.affiliation: Department of Neuroscience and Regenerative Medicine and Department of Neurology.|Charlie Norwood VA Medical Center, Augusta, GA 30912, USA.
authors.forename: Lin
authors.initials: L
authors.lastname: Mei
authors.affiliation: Department of Neuroscience and Regenerative Medicine and Department of Neurology.|Charlie Norwood VA Medical Center, Augusta, GA 30912, USA.
authors.forename: Wen-Cheng
authors.initials: WC
authors.lastname: Xiong
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D001253:Astrocytes / Q000378:metabolism*; D001812:Blood-Brain Barrier / Q000378:metabolism; D018797:Cell Cycle Proteins; D049109:Cell Proliferation; D002478:Cells, Cultured; D005911:Gliosis / Q000378:metabolism*; D018836:Inflammation Mediators / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D017628:Microglia / Q000378:metabolism; D058953:Neural Stem Cells / Q000378:metabolism; D010750:Phosphoproteins / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D000071223:Suppressor of Cytokine Signaling 3 Protein / Q000378:metabolism*; D000091102:YAP-Signaling Proteins
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D018797:Cell Cycle Proteins; D018836:Inflammation Mediators; D010750:Phosphoproteins; C491411:Socs3 protein, mouse; D000071223:Suppressor of Cytokine Signaling 3 Protein; D000091102:YAP-Signaling Proteins; C486223:Yap1 protein, mouse
keywords: SOCS3; STAT3; YAP; blood–brain barrier; reactive astrogliosis