General Medical Information

Transforming Growth Factors

David J. Terris

The TGF family of cytokines is composed of two parental compounds, TGF-a and TGF-b. These two compounds are actually quite distinct; in fact, TGF-a is more closely related to EGF than to TGF-b. All the associated factors in this family are important in the wound-healing process, although TGF-b (which occurs as three distinct isoforms) probably has the most important role and is the most fibrogenic. The TGFs derive their name from the fact that they are able to “transform” normal cells into apparently neoplastic cells. However, they are also known to be mitogenic and chemotactic for epidermal and endothelial cells. TGF-b also stimulates the production of fibronectin, glycosaminoglycans, and collagen. TGFs are secreted by a variety of cells and tissues, including platelets, macrophages, keratinocytes, T lymphocytes, and neutrophils. They exert their effects by binding to receptors, causing activation of the tyrosine kinase cascade. There is experimental evidence to suggest that TGF-b may accelerate wound healing when applied topically. The beneficial effects imparted by TGF-b are realized with or without the addition of radiation. Excessive TGF-b levels, however, may induce pathologic fibrosis. This limitation must be acknowledged as clinical trials are contemplated.