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タイトル: Homeobox A4 suppresses vascular remodeling by repressing YAP/TEAD transcriptional activity
著者: Kimura, Masahiro
Horie, Takahiro  kyouindb  KAKEN_id
Baba, Osamu  kyouindb  KAKEN_id
Ide, Yuya
Tsuji, Shuhei
Ruiz Rodriguez, Randolph
Watanabe, Toshimitsu
Yamasaki, Tomohiro
Otani, Chiharu
Xu, Sijia
Miyasaka, Yui
Nakashima, Yasuhiro  kyouindb  KAKEN_id
Kimura, Takeshi
Ono, Koh
著者名の別形: 木村, 昌弘
堀江, 貴裕
馬場, 理
井手, 裕也
中島, 康弘
木村, 剛
尾野, 亘
発行日: 3-Apr-2020
出版者: Wiley-VCH Verlag
誌名: EMBO Reports
巻: 21
号: 4
論文番号: e48389
抄録: 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.
著作権等: © 2020 The Authors. Published under the terms of the CC BY 4.0 license
URI: http://hdl.handle.net/2433/259304
DOI(出版社版): 10.15252/embr.201948389
PubMed ID: 32147946
出現コレクション:学術雑誌掲載論文等

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