Structure, function and possible clinical application of transforming growth factor-beta

Transforming growth factor-beta (TGF-beta) is a family of multifunctional 25 kDa proteins. TGF-beta was originally identified because of its ability to induce the growth of normal rodent fibroblasts in soft agar, but is now known as a potent growth inhibitor for many different cell types. In addition, TGF-beta is known to regulate the differentiation of cells, induce chemotaxis of cells, and to induce the accumulation of extracellular matrix proteins. In vivo, TGF-beta stimulates the repair of soft as well as hard tissues. It also acts as a potent immunosuppressant. TGF-beta is produced as latent high molecular weight complexes; since it is produced by many different cell types, and most cells have receptors for TGF-beta, the activation of latent TGF-beta is likely to be an important step in the regulation of its action. TGF-beta exerts its effects by binding to specific cell surface receptors. The type I and type II TGF-beta receptors are suggested to be the most important for signal transduction; a recent report has disclosed that the type II receptor has a serine/threonine kinase domain. Since TGF-beta is a potent growth regulator with multifunctional activity, it may be useful in the treatment of certain clinical disorders. Local application of TGF-beta is shown to accelerate wound healing. Since an increase in TGF-beta activity is often observed in various fibrotic disorders, antagonists for TGF-beta might be valuable in the treatment of such diseases.