Increased type II transforming growth factor-beta receptor expression in liver cells during cholesterol challenge.
A large body of evidences implicates transforming growth factor-beta (TGF-beta) in the pathogenesis of atherosclerosis. In this context, TGF-beta receptor dysfunction has been suggested to be relevant. We tested the effect of hypercholesterolemia, a well-known risk factor for atherosclerosis, on liver type II TGF-beta receptor (TbetaR-II) expression in atherosclerosis-susceptible C57BL/6 mouse strain fed atherogenic diet. In addition, the relationship between cholesterol and TbetaR-II expression was verified by cholesterol challenge on human hepatoma cell (HepG2) cultures. The susceptible C57BL/6 mice fed atherogenic diet exhibited significant mRNA and immunohistochemical TbetaR-II liver expression at 2, 5, 9 and 15 weeks as compared to animals fed a regular diet. The TbetaR-II profile on HepG2 resulted in a time-dependent increased expression when the cells were incubated with soluble free cholesterol, associated with an increased TGF-beta-dependent biological activity as detected by luciferase assay of reporter gene. These data provide evidence for a cholesterol-dependent TbetaR-II induction that may play a potentially relevant role in the development of hypercholesterolemia and atherogenesis.
Baccante
G
G
Department of Internal Medicine, University of Chieti, Medical School, Chieti, Italy.
Mincione
G
G
Di Febbo
C
C
Coppa
A
A
Angelucci
D
D
Lapenna
D
D
Cuccurullo
F
F
Colletta
G
G
Porreca
E
E
D000704:Analysis of Variance; D000818:Animals; D001161:Arteriosclerosis / Q000378:metabolism / Q000473:pathology; D015152:Blotting, Northern; D015153:Blotting, Western; D002478:Cells, Cultured; D002784:Cholesterol / Q000378:metabolism*; D004036:Diet, Atherogenic; D022781:Hepatocytes / Q000187:drug effects / Q000378:metabolism*; D007150:Immunohistochemistry; D051379:Mice; D008810:Mice, Inbred C57BL; D023421:Models, Animal; D011336:Probability; D018125:Receptors, Transforming Growth Factor beta / Q000032:analysis*; D012016:Reference Values; D012680:Sensitivity and Specificity; D018709:Statistics, Nonparametric; D015854:Up-Regulation / Q000502:physiology*
D018125:Receptors, Transforming Growth Factor beta; D002784:Cholesterol