The opposing effects of basic fibroblast growth factor and transforming growth factor beta on the regulation of plasminogen activator activity in capillary endothelial cells

Abstract

Basic fibroblast growth factor (bFGF), a potent inducer of angiogenesis in vivo, stimulates the production of both urokinase- and tissue-type plasminogen activators (PAs) in cultured bovine capillary endothelial cells. The observed increase in proteolytic activity induced by bFGF was effectively diminished by picogram amounts of transforming growth factor beta (TGFβ), but could not be abolished by increasing the amount of TGFβ. However, the inhibition by TGFβ was greatly enhanced if the cells were pretreated with TGFβ before addition of bFGF. After prolonged incubation of cultures treated simultaneously with bFGF and TGFβ, the inhibitory effect of TGFβ diminished and the stimulatory effect of the added bFGF dominated as assayed by PA levels. TGFβ did not alte the receptor binding of labeled bFGF, nor did a 6-h pretreatment with TGFβ reduce the amount of bFGF bound. The major difference between the effects of bFGF and TGF̄ was that while bFGF effectively enhanced PA activity expressed by the cells, TGFβ decreased the amounts of both cell-associated and secreted PA activity by decreasing enzyme production. Both bFGF and TGFβ increased in secretion of the endothelial-type plasminogen activator inhibitor.