FIG. 4.

ROS stimulates myofibroblast differentiation and fibrosis. TGFβ1, the EDA-splice variant of fibronectin and mechanical tension are well-known stimuli for myofibroblast differentiation, in which fibroblasts differentiate first into proto-myofibroblasts and further into myofibroblasts, which are characterized by increased expression of αSMA with intense formation of stress fibers, and by an excess synthesis and deposition of ECM, respectively. This fibrotic reaction is typical of inflammation elicited by leukocytes via ROS. Pathologically, the fibrotic environment of desmoplastic tumors supports tumor cell progression. Tumor cells also produce ROS, which stimulate the myofibroblast differentiation of additional fibroblasts. Thus, ROS act as an alternative stimulus for fibrosis, including the characteristic upregulation of ECM production. TGFβ1, transforming growth factor-β1; αSMA, α-smooth muscle actin; EDA, extra domain A.