Concurrent YAP/TAZ and SMAD signaling mediate vocal fold fibrosis

Abstract Vocal fold (VF) fibrosis is a major cause of intractable voice-related disability and reduced quality of life. Excision of fibrotic regions is suboptimal and associated with scar recurrence and/or further iatrogenic damage. Non-surgical interventions are limited, putatively related to limit...

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Autores principales:	Ryosuke Nakamura, Nao Hiwatashi, Renjie Bing, Carina P. Doyle, Ryan C. Branski
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/dbec92e0fd3d4248a6d8406d315a86f9
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spelling	oai:doaj.org-article:dbec92e0fd3d4248a6d8406d315a86f92021-12-02T16:10:27ZConcurrent YAP/TAZ and SMAD signaling mediate vocal fold fibrosis10.1038/s41598-021-92871-z2045-2322https://doaj.org/article/dbec92e0fd3d4248a6d8406d315a86f92021-06-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-92871-zhttps://doaj.org/toc/2045-2322Abstract Vocal fold (VF) fibrosis is a major cause of intractable voice-related disability and reduced quality of life. Excision of fibrotic regions is suboptimal and associated with scar recurrence and/or further iatrogenic damage. Non-surgical interventions are limited, putatively related to limited insight regarding biochemical events underlying fibrosis, and downstream, the lack of therapeutic targets. YAP/TAZ integrates diverse cell signaling events and interacts with signaling pathways related to fibrosis, including the TGF-β/SMAD pathway. We investigated the expression of YAP/TAZ following vocal fold injury in vivo as well as the effects of TGF-β1 on YAP/TAZ activity in human vocal fold fibroblasts, fibroblast-myofibroblast transition, and TGF-β/SMAD signaling. Iatrogenic injury increased nuclear localization of YAP and TAZ in fibrotic rat vocal folds. In vitro, TGF-β1 activated YAP and TAZ in human VF fibroblasts, and inhibition of YAP/TAZ reversed TGF-β1-stimulated fibroplastic gene upregulation. Additionally, TGF-β1 induced localization of YAP and TAZ in close proximity to SMAD2/3, and nuclear accumulation of SMAD2/3 was inhibited by a YAP/TAZ inhibitor. Collectively, YAP and TAZ were synergistically activated with the TGF-β/SMAD pathway, and likely essential for the fibroplastic phenotypic shift in VF fibroblasts. Based on these data, YAP/TAZ may evolve as an attractive therapeutic target for VF fibrosis.Ryosuke NakamuraNao HiwatashiRenjie BingCarina P. DoyleRyan C. BranskiNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-11 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Ryosuke Nakamura Nao Hiwatashi Renjie Bing Carina P. Doyle Ryan C. Branski Concurrent YAP/TAZ and SMAD signaling mediate vocal fold fibrosis
description	Abstract Vocal fold (VF) fibrosis is a major cause of intractable voice-related disability and reduced quality of life. Excision of fibrotic regions is suboptimal and associated with scar recurrence and/or further iatrogenic damage. Non-surgical interventions are limited, putatively related to limited insight regarding biochemical events underlying fibrosis, and downstream, the lack of therapeutic targets. YAP/TAZ integrates diverse cell signaling events and interacts with signaling pathways related to fibrosis, including the TGF-β/SMAD pathway. We investigated the expression of YAP/TAZ following vocal fold injury in vivo as well as the effects of TGF-β1 on YAP/TAZ activity in human vocal fold fibroblasts, fibroblast-myofibroblast transition, and TGF-β/SMAD signaling. Iatrogenic injury increased nuclear localization of YAP and TAZ in fibrotic rat vocal folds. In vitro, TGF-β1 activated YAP and TAZ in human VF fibroblasts, and inhibition of YAP/TAZ reversed TGF-β1-stimulated fibroplastic gene upregulation. Additionally, TGF-β1 induced localization of YAP and TAZ in close proximity to SMAD2/3, and nuclear accumulation of SMAD2/3 was inhibited by a YAP/TAZ inhibitor. Collectively, YAP and TAZ were synergistically activated with the TGF-β/SMAD pathway, and likely essential for the fibroplastic phenotypic shift in VF fibroblasts. Based on these data, YAP/TAZ may evolve as an attractive therapeutic target for VF fibrosis.
format	article
author	Ryosuke Nakamura Nao Hiwatashi Renjie Bing Carina P. Doyle Ryan C. Branski
author_facet	Ryosuke Nakamura Nao Hiwatashi Renjie Bing Carina P. Doyle Ryan C. Branski
author_sort	Ryosuke Nakamura
title	Concurrent YAP/TAZ and SMAD signaling mediate vocal fold fibrosis
title_short	Concurrent YAP/TAZ and SMAD signaling mediate vocal fold fibrosis
title_full	Concurrent YAP/TAZ and SMAD signaling mediate vocal fold fibrosis
title_fullStr	Concurrent YAP/TAZ and SMAD signaling mediate vocal fold fibrosis
title_full_unstemmed	Concurrent YAP/TAZ and SMAD signaling mediate vocal fold fibrosis
title_sort	concurrent yap/taz and smad signaling mediate vocal fold fibrosis
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/dbec92e0fd3d4248a6d8406d315a86f9
work_keys_str_mv	AT ryosukenakamura concurrentyaptazandsmadsignalingmediatevocalfoldfibrosis AT naohiwatashi concurrentyaptazandsmadsignalingmediatevocalfoldfibrosis AT renjiebing concurrentyaptazandsmadsignalingmediatevocalfoldfibrosis AT carinapdoyle concurrentyaptazandsmadsignalingmediatevocalfoldfibrosis AT ryancbranski concurrentyaptazandsmadsignalingmediatevocalfoldfibrosis
_version_	1718384441062064128

Concurrent YAP/TAZ and SMAD signaling mediate vocal fold fibrosis

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