Transforming growth factor-beta up-regulates low density lipoprotein receptor-mediated cholesterol metabolism in vascular smooth muscle cells.
The effects of transforming growth factor-beta (TGF-beta) on low density lipoprotein (LDL) receptor-mediated cholesterol metabolism were evaluated in vascular smooth muscle cells. TGF-beta significantly increased the binding, uptake, and degradation of 125I-LDL. This increase was paralleled by an increase in LDL receptor mRNA steady state levels and an increase in cholesterol esterification. The increase in LDL cholesterol metabolism was independent of proliferation. LDL receptor expression in response to TGF-beta was not affected by coincubation with an antibody against platelet-derived growth factor or by cyclooxygenase inhibitors in arterial smooth muscle cells, suggesting that TGF-beta's effect was not mediated through platelet-derived growth factor or prostaglandins, as demonstrated in other cell systems. However, coincubation with pertussis toxin abrogated the effect of TGF-beta on LDL receptor expression, suggesting that a pertussis toxin-sensitive G-protein may be involved in the signal transduction pathway. These results are discussed in terms of their potential effects on cellular cholesterol trafficking.
Nicholson
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Department of Biochemistry, Cornell University Medical College, New York, New York 10021.
Hajjar
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DP
D000818:Animals; D001011:Aorta / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D002784:Cholesterol / Q000378:metabolism*; D002788:Cholesterol Esters / Q000378:metabolism; D011464:Epoprostenol / Q000378:metabolism; D006801:Humans; D007700:Kinetics; D008077:Lipoproteins, LDL / Q000378:metabolism*; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D037342:Pertussis Toxin; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D011973:Receptors, LDL / Q000096:biosynthesis / Q000187:drug effects / Q000378:metabolism*; D012501:Saphenous Vein / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000494:pharmacology*; D015854:Up-Regulation; D010566:Virulence Factors, Bordetella / Q000494:pharmacology
D002788:Cholesterol Esters; D008077:Lipoproteins, LDL; D012333:RNA, Messenger; D011973:Receptors, LDL; D016212:Transforming Growth Factor beta; D010566:Virulence Factors, Bordetella; D002784:Cholesterol; D011464:Epoprostenol; D037342:Pertussis Toxin