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YAP Is a Critical Inducer of SOCS3, Preventing Reactive Astrogliosis
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 astrocyt...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Oxford University Press
2016
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4830299/ https://www.ncbi.nlm.nih.gov/pubmed/26679195 http://dx.doi.org/10.1093/cercor/bhv292 |
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author | Huang, Zhihui Wang, Ying Hu, Guoqing Zhou, Jiliang Mei, Lin Xiong, Wen-Cheng |
author_facet | Huang, Zhihui Wang, Ying Hu, Guoqing Zhou, Jiliang Mei, Lin Xiong, Wen-Cheng |
author_sort | Huang, Zhihui |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-4830299 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | Oxford University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-48302992016-04-14 YAP Is a Critical Inducer of SOCS3, Preventing Reactive Astrogliosis Huang, Zhihui Wang, Ying Hu, Guoqing Zhou, Jiliang Mei, Lin Xiong, Wen-Cheng Cereb Cortex Articles 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. Oxford University Press 2016-05 2015-12-17 /pmc/articles/PMC4830299/ /pubmed/26679195 http://dx.doi.org/10.1093/cercor/bhv292 Text en © The Author 2015. Published by Oxford University Press. http://creativecommons.org/licenses/by-nc/4.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com |
spellingShingle | Articles Huang, Zhihui Wang, Ying Hu, Guoqing Zhou, Jiliang Mei, Lin Xiong, Wen-Cheng YAP Is a Critical Inducer of SOCS3, Preventing Reactive Astrogliosis |
title | YAP Is a Critical Inducer of SOCS3, Preventing Reactive Astrogliosis |
title_full | YAP Is a Critical Inducer of SOCS3, Preventing Reactive Astrogliosis |
title_fullStr | YAP Is a Critical Inducer of SOCS3, Preventing Reactive Astrogliosis |
title_full_unstemmed | YAP Is a Critical Inducer of SOCS3, Preventing Reactive Astrogliosis |
title_short | YAP Is a Critical Inducer of SOCS3, Preventing Reactive Astrogliosis |
title_sort | yap is a critical inducer of socs3, preventing reactive astrogliosis |
topic | Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4830299/ https://www.ncbi.nlm.nih.gov/pubmed/26679195 http://dx.doi.org/10.1093/cercor/bhv292 |
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