AAV-mediated YAP expression in cardiac fibroblasts promotes inflammation and increases fibrosis

Abstract Fibrosis is a hallmark of heart disease independent of etiology and is thought to contribute to impaired cardiac dysfunction and development of heart failure. However, the underlying mechanisms that regulate the differentiation of fibroblasts to myofibroblasts and fibrotic responses remain...

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Autores principales:	Jamie Francisco, Yu Zhang, Yasuki Nakada, Jae Im Jeong, Chun-Yang Huang, Andreas Ivessa, Shinichi Oka, Gopal J. Babu, Dominic P. Del Re
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/b2840988f77d4ca4a9dc4722061f9f74
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spelling	oai:doaj.org-article:b2840988f77d4ca4a9dc4722061f9f742021-12-02T15:52:47ZAAV-mediated YAP expression in cardiac fibroblasts promotes inflammation and increases fibrosis10.1038/s41598-021-89989-52045-2322https://doaj.org/article/b2840988f77d4ca4a9dc4722061f9f742021-05-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-89989-5https://doaj.org/toc/2045-2322Abstract Fibrosis is a hallmark of heart disease independent of etiology and is thought to contribute to impaired cardiac dysfunction and development of heart failure. However, the underlying mechanisms that regulate the differentiation of fibroblasts to myofibroblasts and fibrotic responses remain incompletely defined. As a result, effective treatments to mitigate excessive fibrosis are lacking. We recently demonstrated that the Hippo pathway effector Yes-associated protein (YAP) is an important mediator of myofibroblast differentiation and fibrosis in the infarcted heart. Yet, whether YAP activation in cardiac fibroblasts is sufficient to drive fibrosis, and how fibroblast YAP affects myocardial inflammation, a significant component of adverse cardiac remodeling, are largely unknown. In this study, we leveraged adeno-associated virus (AAV) to target cardiac fibroblasts and demonstrate that chronic YAP expression upregulated indices of fibrosis and inflammation in the absence of additional stress. YAP occupied the Ccl2 gene and promoted Ccl2 expression, which was associated with increased macrophage infiltration, pro-inflammatory cytokine expression, collagen deposition, and cardiac dysfunction in mice with cardiac fibroblast-targeted YAP overexpression. These results are consistent with other recent reports and extend our understanding of YAP function in modulating fibrotic and inflammatory responses in the heart.Jamie FranciscoYu ZhangYasuki NakadaJae Im JeongChun-Yang HuangAndreas IvessaShinichi OkaGopal J. BabuDominic P. Del ReNature 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 Jamie Francisco Yu Zhang Yasuki Nakada Jae Im Jeong Chun-Yang Huang Andreas Ivessa Shinichi Oka Gopal J. Babu Dominic P. Del Re AAV-mediated YAP expression in cardiac fibroblasts promotes inflammation and increases fibrosis
description	Abstract Fibrosis is a hallmark of heart disease independent of etiology and is thought to contribute to impaired cardiac dysfunction and development of heart failure. However, the underlying mechanisms that regulate the differentiation of fibroblasts to myofibroblasts and fibrotic responses remain incompletely defined. As a result, effective treatments to mitigate excessive fibrosis are lacking. We recently demonstrated that the Hippo pathway effector Yes-associated protein (YAP) is an important mediator of myofibroblast differentiation and fibrosis in the infarcted heart. Yet, whether YAP activation in cardiac fibroblasts is sufficient to drive fibrosis, and how fibroblast YAP affects myocardial inflammation, a significant component of adverse cardiac remodeling, are largely unknown. In this study, we leveraged adeno-associated virus (AAV) to target cardiac fibroblasts and demonstrate that chronic YAP expression upregulated indices of fibrosis and inflammation in the absence of additional stress. YAP occupied the Ccl2 gene and promoted Ccl2 expression, which was associated with increased macrophage infiltration, pro-inflammatory cytokine expression, collagen deposition, and cardiac dysfunction in mice with cardiac fibroblast-targeted YAP overexpression. These results are consistent with other recent reports and extend our understanding of YAP function in modulating fibrotic and inflammatory responses in the heart.
format	article
author	Jamie Francisco Yu Zhang Yasuki Nakada Jae Im Jeong Chun-Yang Huang Andreas Ivessa Shinichi Oka Gopal J. Babu Dominic P. Del Re
author_facet	Jamie Francisco Yu Zhang Yasuki Nakada Jae Im Jeong Chun-Yang Huang Andreas Ivessa Shinichi Oka Gopal J. Babu Dominic P. Del Re
author_sort	Jamie Francisco
title	AAV-mediated YAP expression in cardiac fibroblasts promotes inflammation and increases fibrosis
title_short	AAV-mediated YAP expression in cardiac fibroblasts promotes inflammation and increases fibrosis
title_full	AAV-mediated YAP expression in cardiac fibroblasts promotes inflammation and increases fibrosis
title_fullStr	AAV-mediated YAP expression in cardiac fibroblasts promotes inflammation and increases fibrosis
title_full_unstemmed	AAV-mediated YAP expression in cardiac fibroblasts promotes inflammation and increases fibrosis
title_sort	aav-mediated yap expression in cardiac fibroblasts promotes inflammation and increases fibrosis
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/b2840988f77d4ca4a9dc4722061f9f74
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AAV-mediated YAP expression in cardiac fibroblasts promotes inflammation and increases fibrosis

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