A20 suppresses canonical Smad-dependent fibroblast activation: novel function for an endogenous inflammatory modulator.

ABSTRACT:

Background

The ubiquitin-editing cytosolic enzyme A20, the major negative regulator of toll-like receptor (TLR)-mediated cellular inflammatory responses, has tight genetic linkage with systemic sclerosis (SSc). Because recent studies implicate endogenous ligand-driven TLR signaling in SSc pathogenesis, we sought to investigate the regulation, role and mechanism of action of A20 in skin fibroblasts.

Method

A20 expression and the effects of forced A20 expression or siRNA-mediated A20 knockdown on fibrotic responses induced by transforming growth factor-ß (TGF-ß) were evaluated was evaluated in explanted human skin fibroblasts. Additionally, A20 regulation by TGF-ß, and by adiponectin, a pleiotropic adipokine with anti-fibrotic activity, was evaluated.

Results

In normal

SUBMITTER: Bhattacharyya S 

PROVIDER: S-EPMC5048449 | biostudies-literature | 2016 Oct

REPOSITORIES: biostudies-literature