Medical applications of transforming growth factor-beta

Abstract

Transforming growth factor-beta (TGF-beta) proteins and their antagonists have entered clinical trials. These multi-functional regulators of cell growth and differentiation induce extracellular matrix proteins and suppress the immune system making TGF-betas useful in treatment of wounds with impaired healing, mucositis, fractures, ischemia-reperfusion injuries, and autoimmune disease. In diseases such as keloids, glomerulonephritis and pulmonary fibrosis, excessive expression of TGF-beta has been implicated as being responsible for accumulation of detrimental scar tissue. In these conditions, agents that block TGF-beta have prevented or reversed disease. Similarly, in carcinogenesis, blocking TGF-beta activity may be valuable in stimulating an immune response towards metastasis. As these blocking agents receive approval, we will likely have new therapies for previously recalcitrant diseases.

Figure 1

TGF-β latency complex. The structure of the inactive TGF-β complex is shown with the TGF-β dimer interacting with the latency associated peptide (LAP) and the latent TGF-β binding protein (LTBP). Arrow indicates cleavage site.

Figure 2

Structure of TGF-β. The crystal structure of TGF-β is shown. Amino acids important in regulating binding of TGF-β to receptors and binding proteins have been highlighted.