ABSTRACT The transforming growth factor-betas (TGF-βs) which exist in 3 isoforms in mammals have numerous biological effects in vitro. The TGF-βs and their receptors are ubiquitously expressed in vivo and most cells in culture. All of the TGF-βs are synthesized as pre-proteins and are secreted as biologically latent precursors called latent TGF-β (L-TGF-β). L-TGF-βs are unable to interact with their receptors and are therefore biologically inert. The latent nature of TGF-β is inferred by a protein called the latency associated peptide (LAP) that non-covalently associates with TGF-β. The LAP must be removed or confonnationally altered before there is a biological effect of TGF-β. In vitro, a number of physiochemical means and physiological substances can result in generating a biologically active form of TGF-β. The most recognized association of aberrant TGF-β production in human diseases is in disorders characterized by enhanced connective tissue synthesis. Recently, a number of observations suggest that mechanisms of activation of L-TGF-β previously described in vitro may be important in the pathogenesis of fibrotic disorders in vivo. Interfering with the activation of L-TGF-βl in vivo may be promising in developing therapeutic modalities for fibrotic diseases.
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