Post translational activation of latent transforming growth factor beta (L-TGF-beta): clinical implications

Transforming growth factor-betas (TGF-betas) are multifunctional cytokines that exist in 3 isoforms in mammals. The TGF-betas are ubiquitously express ed and all isoforms are secreted as biologically inactive precursors called latent TGF-beta (L-TGF- beta). L-TGF-betas are generally not effective mol ecules because they are unable to interact with their receptors. However, t he removal of or conformational change of the precursor protein called the latency associated peptide (LAP) results in the generation of biologically active TGF- beta. In vitro active TGF-beta has many biological effects but from a clinical point of view one of the most recognized associations of ab errant TGF-beta production is with diseases characterized by enhanced conne ctive tissue synthesis. Recently a number of observations in the context of fibrotic disorders suggest mechanisms of activation of L-TGF-beta1 in vivo . The recognition of mechanisms that activate L-TGF-beta1 in vivo offers th e possibility of interfering with the activation of L-TGF-beta1 for therape utic purposes.