ID | 118934 |
著者 |
Horii, Yuma
Kyushu University
Matsuda, Shoichi
Kyushu University
Toyota, Chikashi
Kyushu University
Morinaga, Takumi
Kyushu University
Nakaya, Takeo
Jichi Medical University
Tsuchiya, Soken
Kumamoto University
Ohmuraya, Masaki
Hyogo College of Medicine
Hironaka, Takanori
Kyushu University
Yoshiki, Ryo
Kyushu University
Kasai, Kotaro
Kyushu University
Yamauchi, Yuto
Kyushu University
Takizawa, Noburo
Kyushu University
Nagasaka, Akiomi
Kyushu University
Tanaka, Akira
Jichi Medical University
Nakaya, Michio
Kyushu University|Japan Agency for Medical Research and Development
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資料タイプ |
学術雑誌論文
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抄録 | Myofibroblasts cause tissue fibrosis by producing extracellular matrix proteins, such as collagens. Humoral factors like TGF-β, and matrix stiffness are important for collagen production by myofibroblasts. However, the molecular mechanisms regulating their ability to produce collagen remain poorly characterised. Here, we show that vestigial-like family member 3 (VGLL3) is specifically expressed in myofibroblasts from mouse and human fibrotic hearts and promotes collagen production. Further, substrate stiffness triggers VGLL3 translocation into the nucleus through the integrin β1-Rho-actin pathway. In the nucleus, VGLL3 undergoes liquid-liquid phase separation via its low-complexity domain and is incorporated into non-paraspeckle NONO condensates containing EWS RNA-binding protein 1 (EWSR1). VGLL3 binds EWSR1 and suppresses miR-29b, which targets collagen mRNA. Consistently, cardiac fibrosis after myocardial infarction is significantly attenuated in Vgll3-deficient mice, with increased miR-29b expression. Overall, our results reveal an unrecognised VGLL3-mediated pathway that controls myofibroblasts’ collagen production, representing a novel therapeutic target for tissue fibrosis.
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掲載誌名 |
Nature Communications
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ISSN | 20411723
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cat書誌ID | AA12645905
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出版者 | Springer Nature
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巻 | 14
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開始ページ | 550
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発行日 | 2023-02-08
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権利情報 | This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
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言語 |
eng
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著者版フラグ |
出版社版
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部局 |
先端酵素学研究所
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