Shear activates platelet-derived latent TGF-Beta

摘要

Although platelets are a rich source of latent TGF-Beta it has not been determined how plateiet-derived latent TGF-p is activated in vivo. In this issue of Blood, Ahamed and colleagues report that shear and stirring efficiently activate the latent.Platelets release various bioactive sub-stances upon blood clotting, including Platelet-derived growth factor (PDGF) and transforming growth factor (TGF)-Beta. Of the3 TGF-Beta isoforms, TGF-Beta1 is the major iso-form in human platelets. PDGF stimulates the growth of mesenchymal cells, including smooth muscle cells and fibroblasts, whereasTGF-Beta is a potent growth inhibitor for most cell types and induces production of extracellular matrix (ECM) proteins. However, in contrast to other growth factors, bioactivity of TGF-Beta is shielded by the latency-associated peptide (LAP). TGF-P is secreted in latent high-molecular-weight complexes, which require an activation step for exhibiting their functions. Latent TGF-Beta complexes contain 3 components: the active (mature) TGF-Beta dimer, LAP, and the latent TGF-Beta binding protein (LTBP).