Basic fibroblast growth factor-induced low density lipoprotein receptor transcription and surface expression. Signal transduction pathways mediated by the bFGF receptor tyrosine kinase.

摘要: Basic fibroblast growth factor (bFGF) has been implicated in the regulation of cell proliferation and cholesterol metabolism. In studies reported herein, we show bFGF increases low density lipoprotein (LDL) binding, uptake, degradation arterial smooth muscle cells a dose-dependent manner. This increase was paralleled by an LDL receptor mRNA steady state levels. To determine if activated transcription gene, transiently transfected with gene construct consisting 5'-upstream promoter region DNA from human ligated to plasmid containing luciferase gene. We found that protein kinase C (PKC) activator, phorbol 12-myristate 13-acetate, significantly induced activity driven promoter, whereas 25-hydroxycholesterol reduced bFGF-stimulated cells. These findings PKC are inducing transcription. also evaluated potential signal transduction pathways establish mechanism(s) leading activation Activation FGF tyrosine ligand binding resulted phosphorylation one receptors 90-kDa-protein as well increased phospholipase C-gamma. Parallel observations were made A activities occurred compared control Inhibitors other kinases surface expression receptor. Finally, several key enzymes central LDL-cholesteryl ester metabolism studied An acyl-CoA:cholesterol acyltransferase esterification observed stimulation, but there no effect on lysosomal or cytoplasmic cholesteryl hydrolase activities. Our suggest which play role regulating