Regulation and regulatory activities of transforming growth factor beta.

Transforming growth factor beta (TGF beta) is unique among growth factors in its potent and widespread actions. Almost every cell in the body has been shown to make some form of TGF beta, and almost every cell has receptors for TGF beta. Therefore, it becomes apparent that this growth factor must be tightly regulated to prevent disease. The mechanisms of regulation of TGF beta are extensive and complex. One set of mechanisms centers around the fact that TGF beta is produced in a latent form that must be activated to produce biologically active TGF beta. These mechanisms include the latency of the molecule, the production of various latent forms, its targeting to cells for activation or to matrix for storage, and the means of activation of the latent forms. The TGF beta isoforms and the types, affinity, and signaling functions of its receptors also add complexity to the regulation of the effects of TGF beta. Active TGF beta regulates numerous processes in the body. TGF beta has three major biological effects: growth inhibition, stimulation of extracellular matrix formation, and immunosuppression. The means by which TGF beta regulates the expression of the numerous genes on which it has effects are complex and more information is needed. The means by which TGF beta regulates gene expression and the means by which the actions of TGF beta are regulated are addressed in this review.