Adiponectin is an endogenous anti-fibrotic mediator and therapeutic target View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2017-06-30

AUTHORS

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

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. More... »

PAGES

4397

References to SciGraph publications

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  • Identifiers

    URI

    http://scigraph.springernature.com/pub.10.1038/s41598-017-04162-1

    DOI

    http://dx.doi.org/10.1038/s41598-017-04162-1

    DIMENSIONS

    https://app.dimensions.ai/details/publication/pub.1087305643

    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/28667272


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