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-b eta) in the pathogenesis of atherosclerosis. In this context, TGF-beta rece ptor dysfunction has been suggested to be relevant. We tested the effect of hypercholesterolemia. a well-known risk factor for atherosclerosis, on liv er type II TGF-beta receptor (T beta R-II) expression in atherosclerosis-su sceptible C57BL/6 mouse strain fed atherogenic diet. In addition, the relat ionship between cholesterol and T beta R-II expression was verified by chol esterol challenge on human hepatoma cell (HepG2) cultures. The susceptible C57BL/6 mice fed atherogenic diet exhibited significant mRNA and immunohist ochemical T beta R-II liver expression at 2. 5. 9 and 15 weeks as compared to animals fed a regular diet. The T beta R-II profile on HepG2 resulted in a time-dependent increased expression when the cells were incubated with s oluble free cholesterol. associated with an increased TGF-beta-dependent bi ological activity as detected by luciferase assay of reporter gene. These d ata provide evidence for a cholesterol-dependent T beta R-II induction that may play a potentially relevant role in the development of hypercholestero lemia and atherogenesis. (C) 2000 Elsevier Science Ireland Ltd. All rights reserved.