【摘 要】
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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.Her
【机 构】
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Department of Neuroscience and Regenerative Medicine and Department of Neurology;Neuroscience,Wenzho
【出 处】
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第九届海内外华人神经科学家研讨会(The 9th Symposium for Chinese Neuroscientis
论文部分内容阅读
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 brainselective 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.
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