The hard problem: Mechanotransduction perpetuates the myofibroblast phenotype in scleroderma fibrosis.

The effector cells ultimately responsible for fibrosis are myofibroblasts. In the fibrotic autoimmune connective tissue disease scleroderma, myofibroblasts are autonomously activated, and retain their phenotype upon culturing. Since the 1990s, researchers have exploited this fact to use scleroderma fibroblasts as a model system to uncover the fundamental mechanisms underlying myofibroblast persistence in fibrotic conditions. These studies have suggested that an autocrine transforming growth factor (TGF)beta signaling loop is insufficient to explain the persistent myofibroblast phenotype but instead support the hypothesis that fibrotic myofibroblasts possess an intrinsically activated pro-adhesive signaling pathway, and that this contributes to the perpetuation of pathological fibrosis. This review focuses on these observations.