Effects of TGF-β1 on endothelial factors

This study investigated the mechanistic effect of transforming growth factor-beta1 (TGFβ1) on the endothelial mediators: endothelin-1 (ET-1), prostacyclin (PGI2) and nitric oxide (NO) in the endothelial cell line 1G11. Endothelial cells were incubated with increasing concentrations of TGFβ1 in the presence and absence of growth medium (deprived) or various inhibitors. In deprived cells, TGFβ1 increased the release of PGI2 (6-keto-PGF1α) concomitantly to an increase in COX-2 expression, whereas the production of ET-1 and NO metabolites was not affected. Either the removal of prior serum and heparin deprivation or NO synthase inhibition by L-NAME unmasked an inhibitory effect of TGFβ1 on ET-1 production. Indomethacin abolished the TGFβ1 inhibitory action on L-NAME-increased ET-1 production. These results show that TGFβ1 induces an increase in production of PGI2 that is consecutive to an induction of COX-2 in endothelial cells. This increase in PGI2 partly accounts for the inhibitory action of TGFβ1 on ET-1 secretion.

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