Increased type II transforming growth factor-β receptor expression in liver cells during cholesterol challenge

A large body of evidences implicates transforming growth factor-β (TGF-β) in the pathogenesis of atherosclerosis. In this context, TGF-β 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-β receptor (TβR-II) expression in atherosclerosis-susceptible C57BL/6 mouse strain fed atherogenic diet. In addition, the relationship between cholesterol and TβR-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 TβR-II liver expression at 2, 5, 9 and 15 weeks as compared to animals fed a regular diet. The TβR-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-β-dependent biological activity as detected by luciferase assay of reporter gene. These data provide evidence for a cholesterol-dependent TβR-II induction that may play a potentially relevant role in the development of hypercholesterolemia and atherogenesis.