Fibronectin signaling via toll-like receptprs: a novel paradigm for persistent fibrosis in scleroderma

Abstract

Scleroderma is a systemic autoimmune disease with unknown etiology. Fibrosis, the hallmark of scleroderma, is the transformation of self-limited wound healing into a self-sustaining non-healing process. The factors responsible for maintaining persistent fibroblast activation in scleroderma and other conditions with chronic fibrosis are not well understood. We recently showed that TLR4 and fibronectin extra domain A (Fn^EDA), an endogenous TLR4 ligand, both are markedly elevated in the lesional skin biopsies from scleroderma patients and were shown to be involved in scleroderma disease pathogenesis. Here, we highlight the role of the Fn^EDA-TLR4 signaling axis in fibrosis, and the mechanisms involved in driving persistence of fibrosis in scleroderma.