Figure 1.

Principal cellular events leading to fibrosis. Injury to epithelial cells results in their release of pro-inflammatory cytokines, which is a stimulus for infiltration of macrophages and immune cells to the injury site. This results in an inflammatory environment in which cytokines, chemokines, and growth factors are produced that drive the production and action of contractile αSMA-producing myofibroblasts. Myofibroblasts arise by activation of resident fibroblasts or circulating fibrocytes or are the result of transdifferentiation from other cell types such as epithelial cells, endothelial cells, or pericytes. In acute injury, myofibroblasts transiently produce ECM components such as collagen, laminin, and FN which are necessary for normal wound healing, and parenchymal repopulation. During persistent or recurrent episodic injury, the inflammatory phase is protracted leading to unrelenting myofibroblastic activity, which is manifested as excessive production of ECM components that are deposited in the interstitial space as scar material, or fibrosis.