Adiponectin is an endogenous anti-fibrotic mediator and therapeutic target

Abstract Skin fibrosis in systemic sclerosis (SSc) is accompanied by attrition of dermal white adipose tissue (dWAT) and reduced levels of circulating adiponectin. Since adiponectin has potent regulatory effects on fibroblasts, we sought to assess adiponectin signaling in SSc skin biopsies, and eval...

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Autores principales:	Roberta G. Marangoni, Yuri Masui, Feng Fang, Benjamin Korman, Gabriel Lord, Junghwa Lee, Katja Lakota, Jun Wei, Philipp E. Scherer, Laszlo Otvos, Toshimasa Yamauchi, Naoto Kubota, Takashi Kadowaki, Yoshihide Asano, Shinichi Sato, Warren G. Tourtellotte, John Varga
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/6f36cafe22ea4bf78193c98c31cf6636
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spelling	oai:doaj.org-article:6f36cafe22ea4bf78193c98c31cf66362021-12-02T15:05:21ZAdiponectin is an endogenous anti-fibrotic mediator and therapeutic target10.1038/s41598-017-04162-12045-2322https://doaj.org/article/6f36cafe22ea4bf78193c98c31cf66362017-06-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-04162-1https://doaj.org/toc/2045-2322Abstract Skin fibrosis in systemic sclerosis (SSc) is accompanied by attrition of dermal white adipose tissue (dWAT) and reduced levels of circulating adiponectin. Since adiponectin has potent regulatory effects on fibroblasts, we sought to assess adiponectin signaling in SSc skin biopsies, and evaluate fibrosis in mice with adiponectin gain- and loss-of-function mutations. Furthermore, we investigated the effects and mechanism of action of agonist peptides targeting adiponectin receptors in vitro and in vivo. We found that adiponectin pathway activity was significantly reduced in a subset of SSc skin biopsies. Mice lacking adiponectin mounted an exaggerated dermal fibrotic response, while transgenic mice with constitutively elevated adiponectin showed selective dWAT expansion and protection from skin and peritoneal fibrosis. Adiponectin receptor agonists abrogated ex vivo fibrotic responses in explanted normal and SSc fibroblasts and in 3D human skin equivalents, in part by attenuating focal adhesion complex assembly, and prevented and reversed experimentally-induced organ fibrosis in mice. These results implicate aberrant adiponectin pathway activity in skin fibrosis, identifying a novel function for this pleiotropic adipokine in regulation of tissue remodeling. Restoring adiponectin signaling in SSc patients therefore might represent an innovative pharmacological strategy for intractable organ fibrosis.Roberta G. MarangoniYuri MasuiFeng FangBenjamin KormanGabriel LordJunghwa LeeKatja LakotaJun WeiPhilipp E. SchererLaszlo OtvosToshimasa YamauchiNaoto KubotaTakashi KadowakiYoshihide AsanoShinichi SatoWarren G. TourtellotteJohn VargaNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-12 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Roberta G. Marangoni Yuri Masui Feng Fang Benjamin Korman Gabriel Lord Junghwa Lee Katja Lakota Jun Wei Philipp E. Scherer Laszlo Otvos Toshimasa Yamauchi Naoto Kubota Takashi Kadowaki Yoshihide Asano Shinichi Sato Warren G. Tourtellotte John Varga Adiponectin is an endogenous anti-fibrotic mediator and therapeutic target
description	Abstract Skin fibrosis in systemic sclerosis (SSc) is accompanied by attrition of dermal white adipose tissue (dWAT) and reduced levels of circulating adiponectin. Since adiponectin has potent regulatory effects on fibroblasts, we sought to assess adiponectin signaling in SSc skin biopsies, and evaluate fibrosis in mice with adiponectin gain- and loss-of-function mutations. Furthermore, we investigated the effects and mechanism of action of agonist peptides targeting adiponectin receptors in vitro and in vivo. We found that adiponectin pathway activity was significantly reduced in a subset of SSc skin biopsies. Mice lacking adiponectin mounted an exaggerated dermal fibrotic response, while transgenic mice with constitutively elevated adiponectin showed selective dWAT expansion and protection from skin and peritoneal fibrosis. Adiponectin receptor agonists abrogated ex vivo fibrotic responses in explanted normal and SSc fibroblasts and in 3D human skin equivalents, in part by attenuating focal adhesion complex assembly, and prevented and reversed experimentally-induced organ fibrosis in mice. These results implicate aberrant adiponectin pathway activity in skin fibrosis, identifying a novel function for this pleiotropic adipokine in regulation of tissue remodeling. Restoring adiponectin signaling in SSc patients therefore might represent an innovative pharmacological strategy for intractable organ fibrosis.
format	article
author	Roberta G. Marangoni Yuri Masui Feng Fang Benjamin Korman Gabriel Lord Junghwa Lee Katja Lakota Jun Wei Philipp E. Scherer Laszlo Otvos Toshimasa Yamauchi Naoto Kubota Takashi Kadowaki Yoshihide Asano Shinichi Sato Warren G. Tourtellotte John Varga
author_facet	Roberta G. Marangoni Yuri Masui Feng Fang Benjamin Korman Gabriel Lord Junghwa Lee Katja Lakota Jun Wei Philipp E. Scherer Laszlo Otvos Toshimasa Yamauchi Naoto Kubota Takashi Kadowaki Yoshihide Asano Shinichi Sato Warren G. Tourtellotte John Varga
author_sort	Roberta G. Marangoni
title	Adiponectin is an endogenous anti-fibrotic mediator and therapeutic target
title_short	Adiponectin is an endogenous anti-fibrotic mediator and therapeutic target
title_full	Adiponectin is an endogenous anti-fibrotic mediator and therapeutic target
title_fullStr	Adiponectin is an endogenous anti-fibrotic mediator and therapeutic target
title_full_unstemmed	Adiponectin is an endogenous anti-fibrotic mediator and therapeutic target
title_sort	adiponectin is an endogenous anti-fibrotic mediator and therapeutic target
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/6f36cafe22ea4bf78193c98c31cf6636
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Adiponectin is an endogenous anti-fibrotic mediator and therapeutic target

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