Fibronectin Promotes Chronic Cutaneous Fibrosis Through Toll-Like Receptor Signaling

Author: S. Bhattacharyya, Z. Tamaki, W. Wang, M. Hinchcliff, P. Hoover, S. Getsios, E. S. White and J. Varga
Date Published: April-2014
Source: Science

Scleroderma is a progressive autoimmune disease affecting multiple organs. Fibrosis, the hallmark of scleroderma, represents transformation of self-limited wound healing into a deregulated self-sustaining process. The factors responsible for maintaining persistent fibroblast activation in scleroderma and other conditions with chronic fibrosis are not well understood. Toll-like receptor 4 (TLR4) and its damage-associated endogenous ligands are implicated in immune and fibrotic responses. We now show that fibronectin extra domain A (FnEDA) is an endogenous TLR4 ligand markedly elevated in the circulation and lesional skin biopsies from patients with scleroderma, as well as in mice with experimentally induced cutaneous fibrosis.