Abstract

During repair of connective tissue, resting fibroblasts become ‘activated’; that is, they migrate into the wound where they synthesize and remodel new extracellular matrix. The differentiated fibroblast responsible for this action is termed the myofibroblast, which expresses the highly contractile protein α—smooth muscle actin (α—SMA) and is responsible for the synthesis and remodeling of extracellular matrix (ECM). Persistence of the myofibroblast is a key characteristic of fibrotic diseases including scleroderma. Proteins such as transforming growth factorβ (TGFβ), endothelin-1 (ET- 1), connective tissue growth factor (CCN2/CTGF) and platelet derived growth factor (PDGF) are believed to contribute to myofibroblast differentiation and persistence. Moreover, it is now known that elevated adhesive and contractile signaling is a key feature of fibrotic fibroblasts. This review summarizes recent findings aimed at developing new, rationally-designed therapies for the fibrosis in scleroderma.

Keywords: PDGF, TGFβ, endothelin, rac, PPARγ, PKCε