Fibroblast growth factor upregulates PGG/H synthase in rabbit microvascular endothelial cells by a glucocorticoid independent mechanism.
The present study was undertaken to determine the effects of acidic fibroblast growth factor (aFGF) on eicosanoid synthesis in microvessel endothelial cells derived from rabbit left ventricular muscle (RCME cells). We observed that aFGF increased AA conversion to PGE2 in a time- and dose-dependent manner, and the stimulatory effect was abolished by actinomycin D and cycloheximide. Acidic FGF increased the recovery of PGG/H synthase activity following aspirin treatment, suggesting an action on de novo PGG/H synthase synthesis. Acidic FGF increased the incorporation of [35S] methionine into a 70 kD immunoreactive PGG/H synthase band. PGG/H synthase synthesis following aspirin treatment was also increased by transforming growth factor beta, while epidermal growth factor basic FGF and platelet derived growth factor were without effect. In addition, the actions of aFGF on de novo PGG/H synthase were compared in several endothelial preparations. Acidic FGF treatment of aspirin treated endothelial cells from rabbit lung microvessels and small pulmonary artery and from human lung microvessels all showed an increase in PGG/H synthase recovery. In contrast, similar treatment of human umbilical vein endothelial cells was without effect. Pretreatment of RCME cells with dexamethasone (1 microM) did not alter the aFGF induction of PGG/H synthase activity. We conclude that aFGF stimulates PGE2 production by a mechanism that includes the de novo synthesis of PGG/H synthase. This mechanism appears to be distinct from previously described glucocorticoid sensitive translational controls of PG synthase synthesis by epidermal growth factor in smooth muscle and mesangial cells.
Moatter
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Department of Physiology, New York Medical College, Valhalla 10595.
Gerritsen
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D000818:Animals; D001241:Aspirin / Q000494:pharmacology; D002196:Capillaries / Q000166:cytology / Q000378:metabolism; D002417:Cattle; D002462:Cell Membrane / Q000378:metabolism; D003513:Cycloheximide / Q000494:pharmacology; D003907:Dexamethasone / Q000494:pharmacology; D015232:Dinoprostone / Q000096:biosynthesis*; D004730:Endothelium, Vascular / Q000378:metabolism*; D005346:Fibroblast Growth Factors / Q000502:physiology*; D006801:Humans; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism*; D011817:Rabbits; D013552:Swine; D015854:Up-Regulation
D005346:Fibroblast Growth Factors; D003907:Dexamethasone; D003513:Cycloheximide; D011451:Prostaglandin-Endoperoxide Synthases; D015232:Dinoprostone; D001241:Aspirin