YAP Is a Critical Inducer of SOCS3, Preventing Reactive Astrogliosis

Zhihui Huang, Ying Wang, Guoqing Hu, Jiliang Zhou, Lin Mei, Wencheng Xiong

Research output: Contribution to journalArticle

34 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)2299-2310
Number of pages12
JournalCerebral Cortex
Volume26
Issue number5
DOIs
StatePublished - May 1 2016

Keywords

  • SOCS3
  • STAT3
  • YAP
  • blood-brain barrier
  • reactive astrogliosis

ASJC Scopus subject areas

  • Cognitive Neuroscience
  • Cellular and Molecular Neuroscience

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