Focal Adhesion Kinase: A Key Mediator of Transforming Growth Factor Beta Signaling in Fibroblasts
Author:
- 1 June 2013
- journal article
- review article
- Published by SAGE Publications in Advances in Wound Care
- Vol. 2 (5) , 247-249
Abstract
Significance: There is no effective drug therapy for scarring and fibrotic disease. The cytokine transforming growth factor beta (TGF-β) promotes tissue repair, but its excessive action can lead to over exuberant scarring and fibrotic disease. However, owing to the multifunctional nature of TGF-β, broad targeting of the canonical Smad–TGF-β signaling pathway in vivo is likely to have unintended, deleterious consequences. Recent Advances: (1) The myofibroblast is the essential cell type that mediates tissue repair and fibrosis. (2) TGF-β is an essential contributor to myofibroblast differentiation and activity. (3) TGF-β selectively promotes tissue repair and fibrosis via the noncanonical focal adhesion kinase (FAK) pathway; FAK mediates myofibroblast differentiation, and hence may represent a novel intervention point for drugs treating fibrotic disease. Critical Issues: Excessive scarring (e.g., in hypertrophic scars, keloids, and scleroderma) is characterized by enhanced TGF-β signaling and is a major clinical problem. Drugs that selectively and effectively control the profibrotic action of TGF-β is therefore of clinical relevance. Future Directions: FAK inhibition may represent a novel therapy for scarring disorders.Keywords
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