Figure 4.

Fibrosis. ECM metabolism and turnover is dependent on the function of fibroblasts, MMPs, TIMPs, and the local tissue environment (A). TIMPs regulate MMP activity and directly inhibit ECM degradation, and the increase of TIMP function and release of TGF-β1 results in excessive ECM deposition (B). In addition, activated (myo)fibroblasts express integrin receptors that connect TGF-β1 and ECM components, resulting in fibrotic tissue with denser and straighter ECM fibers, which eventually leads to overall higher tissue stiffness. At this point, even smaller mechanical stresses applied to the fibrotic tissue will cause the release of more TGF-β1 (C).