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dc.contributor.author | Kimura, Masahiro | en |
dc.contributor.author | Horie, Takahiro | en |
dc.contributor.author | Baba, Osamu | en |
dc.contributor.author | Ide, Yuya | en |
dc.contributor.author | Tsuji, Shuhei | en |
dc.contributor.author | Ruiz Rodriguez, Randolph | en |
dc.contributor.author | Watanabe, Toshimitsu | en |
dc.contributor.author | Yamasaki, Tomohiro | en |
dc.contributor.author | Otani, Chiharu | en |
dc.contributor.author | Xu, Sijia | en |
dc.contributor.author | Miyasaka, Yui | en |
dc.contributor.author | Nakashima, Yasuhiro | en |
dc.contributor.author | Kimura, Takeshi | en |
dc.contributor.author | Ono, Koh | en |
dc.contributor.alternative | 木村, 昌弘 | ja |
dc.contributor.alternative | 堀江, 貴裕 | ja |
dc.contributor.alternative | 馬場, 理 | ja |
dc.contributor.alternative | 井手, 裕也 | ja |
dc.contributor.alternative | 中島, 康弘 | ja |
dc.contributor.alternative | 木村, 剛 | ja |
dc.contributor.alternative | 尾野, 亘 | ja |
dc.date.accessioned | 2020-11-30T02:47:45Z | - |
dc.date.available | 2020-11-30T02:47:45Z | - |
dc.date.issued | 2020-04-03 | - |
dc.identifier.issn | 1469-221X | - |
dc.identifier.issn | 1469-3178 | - |
dc.identifier.uri | http://hdl.handle.net/2433/259304 | - |
dc.description.abstract | The Hippo signaling pathway is involved in the pathophysiology of various cardiovascular diseases. Yes‐associated protein (YAP) and transcriptional enhancer activator domain (TEAD) transcriptional factors, the main transcriptional complex of the Hippo pathway, were recently identified as modulators of phenotypic switching of vascular smooth muscle cells (VSMCs). However, the intrinsic regulator of YAP/TEAD‐mediated gene expressions involved in vascular pathophysiology remains to be elucidated. Here, we identified Homeobox A4 (HOXA4) as a potent repressor of YAP/TEAD transcriptional activity using lentiviral shRNA screen. Mechanistically, HOXA4 interacts with TEADs and attenuates YAP/TEAD‐mediated transcription by competing with YAP for TEAD binding. We also clarified that the expression of HOXA4 is relatively abundant in the vasculature, especially in VSMCs. In vitro experiments in human VSMCs showed HOXA4 maintains the differentiation state of VSMCs via inhibition of YAP/TEAD‐induced phenotypic switching. We generated Hoxa4‐deficient mice and confirmed the downregulation of smooth muscle‐specific contractile genes and the exacerbation of vascular remodeling after carotid artery ligation in vivo. Our results demonstrate that HOXA4 is a repressor of VSMC phenotypic switching by inhibiting YAP/TEAD‐mediated transcription. | en |
dc.format.mimetype | application/pdf | - |
dc.language.iso | eng | - |
dc.publisher | Wiley-VCH Verlag | en |
dc.rights | © 2020 The Authors. Published under the terms of the CC BY 4.0 license | en |
dc.title | Homeobox A4 suppresses vascular remodeling by repressing YAP/TEAD transcriptional activity | en |
dc.type | journal article | - |
dc.type.niitype | Journal Article | - |
dc.identifier.jtitle | EMBO Reports | en |
dc.identifier.volume | 21 | - |
dc.identifier.issue | 4 | - |
dc.relation.doi | 10.15252/embr.201948389 | - |
dc.textversion | publisher | - |
dc.identifier.artnum | e48389 | - |
dc.identifier.pmid | 32147946 | - |
dcterms.accessRights | open access | - |
datacite.awardNumber | 17H04177 | - |
datacite.awardNumber | 17H05599 | - |
datacite.awardNumber | 17K19590 | - |
datacite.awardNumber | 17K09860 | - |
datacite.awardNumber | JP1605297 | - |
dc.identifier.pissn | 1469-221X | - |
dc.identifier.eissn | 1469-3178 | - |
jpcoar.funderName | 日本学術振興会 | ja |
jpcoar.funderName | 日本学術振興会 | ja |
jpcoar.funderName | 日本学術振興会 | ja |
jpcoar.funderName | 日本学術振興会 | ja |
jpcoar.funderName | 日本学術振興会 | ja |
jpcoar.funderName.alternative | Japan Society for the Promotion of Science (JSPS) | en |
jpcoar.funderName.alternative | Japan Society for the Promotion of Science (JSPS) | en |
jpcoar.funderName.alternative | Japan Society for the Promotion of Science (JSPS) | en |
jpcoar.funderName.alternative | Japan Society for the Promotion of Science (JSPS) | en |
jpcoar.funderName.alternative | Japan Society for the Promotion of Science (JSPS) | en |
出現コレクション: | 学術雑誌掲載論文等 |
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