Adiponectin is an endogenous anti-fibrotic mediator and therapeutic target

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

Research output: Contribution to journalArticlepeer-review

34 Scopus citations

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.

Original languageEnglish (US)
Article number4397
JournalScientific reports
Volume7
Issue number1
DOIs
StatePublished - Dec 1 2017

ASJC Scopus subject areas

  • General

Fingerprint

Dive into the research topics of 'Adiponectin is an endogenous anti-fibrotic mediator and therapeutic target'. Together they form a unique fingerprint.

Cite this