Hypothesis: pathogenesis of systemic sclerosis.

A hypothesis for the pathogenesis of systemic sclerosis (SSc) is proposed. Transforming growth factor-beta (TGF-beta) has received attention as an essential factor in the pathogenesis of various fibrotic disorders, including SSc, although some unknown additional factor has been sought as the second mediator of fibrotic disorders. Connective tissue growth factor (CTGF) has been shown to be closely related to the pathogenesis of SSc as follows: (1) CTGF mRNA expression was observed in the fibrotic lesions but not in the early nonfibrotic lesions or atrophic lesions. (2) Serum CTGF protein concentrations were significantly elevated, and correlated with skin sclerosis and lung fibrosis. (3) In our animal model, TGF-beta-induced subcutaneous fibrosis and subsequent CTGF application caused persistent fibrosis. Based on these data, we hypothesize that a 2-step process of fibrosis occurs in SSc: that is, TGF-beta induces fibrosis in the early stage and afterwards CTGF acts to maintain tissue fibrosis.