Fig. 2.
Transition of healthy tissue to fibrotic tissue. A proposed sequence of events highlighting a stepwise remodeling of the ECM that involves alterations in the composition of the ECM and effects on cell phenotype that eventually result in tissue fibrosis. A central component in this pathway is the temporal generation of the major collagen-secreting cell, the myofibroblast, from resident fibroblasts. As an alternative pathway, circulating cells such as fibrocytes or other stem cells may directly engraft into tissue and transdifferentiate into myofibroblasts, promoting fibrosis. TGF-β, transforming growth factor-β; CTGF, connective tissue growth factor.