Abstract

Excessive extracellular matrix deposition in the skin, lung, and other organs is a hallmark of systemic sclerosis (SSc). Fibroblasts isolated from sclerotic lesions in patients with SSc and cultured in vitro are characterized by increased synthesis of collagen and other extracellular matrix components, consistent with the disease phenotype. Thus, cultured scleroderma fibroblasts serve as a principal experimental model for studying the mechanisms involved in extracellular matrix overproduction in SSc. The pathogenesis of SSc is still poorly understood, but increasing evidence suggests that transforming growth factor-beta (TGF-beta) is a key mediator of tissue fibrosis as a consequence of extracellular matrix accumulation in the pathology of SSc. TGF-beta regulates diverse biological activities including cell growth, cell death or apoptosis, cell differentiation, and extracellular matrix synthesis. TGF-beta is known to induce the expression of extracellular matrix proteins in mesenchymal cells and to stimulate the production of protease inhibitors that prevent enzymatic breakdown of the extracellular matrix. This review focuses on the possible role of autocrine TGF-beta signaling in the pathogenesis of SSc.