Adipocyte-specific Repression of PPAR-gamma by NCoR Contributes to Scleroderma Skin Fibrosis.

ABSTRACT: BACKGROUND:A pivotal role for adipose tissue homeostasis in systemic sclerosis (SSc) skin fibrosis is increasingly recognized. The nuclear receptor PPAR-? is the master regulator of adipogenesis. Peroxisome proliferator activated receptor-? (PPAR-?) has antifibrotic effects by blocking transforming growth factor-? (TGF-?) and is dysregulated in SSc. To unravel the impact of dysregulated PPAR-? in SSc, we focused on nuclear corepressor (NCoR), which negatively regulates PPAR-? activity and suppresses adipogenesis. METHODS:An NCoR-regulated gene signature was measured in the SSc skin transcriptome. Experimental skin fibrosis was examined in mice with adipocyte-specific NCoR ablation. RESULTS:SSc skin biopsies demonstrated deregulated NCoR signaling. A 43-gene NCoR gene signature showed strong positive correlation with PPAR-? signaling (R?=?0.919, p?

SUBMITTER: Korman B 

PROVIDER: S-EPMC6042240 | biostudies-literature | 2018 Jul

REPOSITORIES: biostudies-literature