Search

Transforming Growth Factor beta 1 (TGFbeta1) is a key cytokine in the development of fibrotic diseases which are characterized by a pathological excess of extracellular matrix involving multiple organs.To induce its biological effects, TGFbeta1 interacts with Ser/Thr kinase receptor complexes. The polypeptide binding to the receptors induces TGFbeta intracellular mediator phosphorylation and namely Smad proteins. Upon phosphorylation the latter form protein complexes which are then translocated to the nucleus where they participate to matrix gene regulation.We will summarize the literature on the involvement of TGFbeta1 through the Smad proteins in fibrotic diseases.

Transforming growth factor-beta (TGF-beta) family members are multifunctional peptide growth factors that regulate cell growth, differentiation, extracellular matrix production and cell migration and embryonic development. Knock-out experiments for the three mammalian isoforms of TGF-beta 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. In the latter case, it may exert both tumor suppressor and pro-oncogenic activities depending on the stage of the tumor. Smads proteins constitute the core components of the intracellular signaling cascade initiated by TGF-beta receptors, as they carry signals from the cell surface directly to the nucleus; where they act as transcription factors.