TGFβ—a role in systemic sclerosis?

Abstract

Systemic sclerosis (SSc) is a multisystem connective tissue disorder in which there is progressive fibrosis. Transforming growth factor beta (TGFβ) has wide‐ranging cellular actions. It is a potent chemoattractant for human dermal fibroblasts, from which it may induce synthesis of collagen, which suggests that it may have a central role to play in the pathogenesis of SSc. This is supported to some extent by in vitro studies. SSc fibroblasts produce more collagens and fibronectin than normal fibroblasts and elevated TIMP levels have been observed, all of which could be explained on the basis of TGFβ stimulation of fibroblasts. Some studies have suggested that fibroblasts are the source of TGFβ. However, the serum of patients with SSc is cytotoxic to endothelial cells, which could culminate in TGFβ synthesis by them, with secondary fibroblast stimulation. The role of TGFβ remains elusive, although it would seem an ideal candidate as a mediator of fibrosis in systemic sclerosis. © 1998 John Wiley & Sons, Ltd.