[Thrombospondin-1-dependent mechanism of transforming growth factor beta-1 activation in cultured human endothelial...

Using two immortal human umbilical vein endothelial-derived cell lines we investigated the thrombospondin-1 (TSP-1)-dependent mechanism of the transforming growth factor beta-1 (TGFbeta1) activation. Exogenous human platelet TSP-1 was demonstrated to increase (1.7-2.0-folds) the concentration of active TGFbeta1 produced by both cell lines, but did not influence the concentration of total TGFbeta1. The process of TGFbeta1 activation is known to be regulated by G418GWSHW423 fragment of TSP-1 molecule. The simultaneous addition of TSP-1 and 100-fold molar excess (about TSP-1) of the synthetic GGWSHW peptide abolished TSP-1-induced TGFbeta1 activation. GGWSHW peptide inhibited the basal activation of TGFbeta1 in endothelial cells, whereas the secretion of total TGFbeta1 and TSP-1 was not altered. We conclude that TSP-1-dependent mechanism of endogenous TGFbeta1 activation is operation in human endothelial cells.