Mediators of fibrosis.

Abstract

Progressive, uncontrolled deposition of extracellular matrix proteins leading to scar tissue formation and organ failure represents a final common pathway of tissue response to chronic injury. The nature of the insult varies between organs and tissues and may include viral infections or toxic agents, but in most cases the specific trigger remains unknown. Extensive research on the mechanisms of fibrosis has greatly contributed to a better understanding of the pathological mechanisms involved in this process. While we are learning more about the pathways that contribute to fibrosis, it would be important to integrate this new information with the large body of existing knowledge on the profibrotic mediators, especially Transforming Growth factor (TGF ). TGF is one of the most potent inducers of extracellular matrix and has long been considered to be a principal mediator of fibrosis. In addition to activation of both Smad-dependent and Smad-independent signaling pathways, TGF is involved in an extensive crosstalk with multiple other cellular pathways. Better understanding of the regulatory networks governing the fibrotic response at the cellular level will help to define the key regulatory molecules and advance the design of logical therapeutic targets. This series of articles will highlight some of the new developments in the field of fibrotic mediators.