Fig. 1.

Development, tissue homeostasis, and response to injury are dependent on ECM expression and deposition. ECM expression and turnover are tightly controlled during organ development and during adulthood. Tissue injury triggers inflammation, clotting, redox stress, and regulated expression and degradation of the ECM. In general, elimination of the injurious agents is followed by ‘turning off’ this wound healing response resulting in inhibition of ECM expression and, ultimately, a return to the original tissue structure and function (Adaptive Repair). However, on occasion, injury triggers an exuberant response characterized by uncontrolled ECM expression and turnover leading to increased stiffness of the tissue and eradication of the original tissue architecture leading to loss of function (Maladaptive Repair). These events are greatly influenced by genetics and environmental exposures. Uncontrolled generation of reactive oxidant species (ROS) is thought to contribute to maladaptive repair, in part, by promoting aberrant ECM expression and fibroproliferation.