Mammalian transforming growth factor-betas: Smad signaling and physio-pathological roles.

Since its discovery in the early 1980s, transforming growth factor-beta (TGF-beta) has emerged as a family of growth factors involved in essential physiological processes, including embryonic development, differentiation, tissue repair and cell growth control. Knockout experiments for the three mammalian isoforms of TGF-betas in mice have demonstrated their importance in regulating inflammation and tissue repair. Also, TGF-beta has been implicated in the pathogenesis of human diseases, including tissue fibrosis and carcinogenesis where, in the latter case, it may exert both tumor suppressor and pro-oncogenic activities depending on the stage of the tumor. Cellular signaling by TGF-beta family members is initiated by the assembly of specific cell surface serine/threonine kinase type receptors that activate transcription factors of the Smad family.