title: The orphan nuclear receptor Nur77 regulates hepatic cholesterol metabolism             through the suppression of LDLR and HMGCR expression.
abstract: Disorders in cholesterol metabolism are critical in development of atherosclerosis and are related to acute myocardial infarction (AMI). The liver is one of the most important organs that balances cholesterol metabolism. In order to investigate whether Nur77 is capable of regulating cholesterol metabolism in HepG2 cells and to demonstrate the underlying mechanism, the downregulation and upregulation of Nur77 expression in HepG2 cells was achieved by the transfection of siRNA specific to Nur77 and the transfection of the recombinant plasmid, pcDNA3.1-Nur77, respectively. Following the downregulation and upregulation of Nur77 expression, changes in the total cholesterol (TCHO) levels in HepG2 cells were observed based on lipid overloading. Thereafter, changes in a series of key gene expressions related to hepatic cholesterol metabolism were measured at the mRNA and protein levels by RT-PCR and western blot analysis, respectively. The TCHO levels in the HepG2 cells were found to increase following the downregulation of Nur77 expression and to decrease following the upregulation of Nur77 expression; these results were confirmed by oil red O staining of the cells. As for the hepatic cholesterol metabolism genes, low-density lipoprotein receptor (LDLR) and HMGCoA reductase (HMGCR) levels increased following the downregulation of Nur77 expression and decreased following the upregulation of Nur77 expression. However, liver X receptor α (LXRα) expression did not change markedly along with that of Nur77. According to these findings, we conclude that Nur77 is capable of reducing hepatic cholesterol based on lipid overloading, and that this may be due to the decrease in LDLR and HMGCR levels.
authors.affiliation: Department of Laboratory Medicine, Nanfang Hospital, Southern Medical University, Guangdong , People's Republic of China.
authors.forename: Peng
authors.initials: P
authors.lastname: Zhang
authors.forename: Yanwei
authors.initials: Y
authors.lastname: Hu
authors.forename: Junyao
authors.initials: J
authors.lastname: Yang
authors.forename: Lei
authors.initials: L
authors.lastname: Zheng
authors.forename: Qian
authors.initials: Q
authors.lastname: Wang
mesh_terms: D002784:Cholesterol / Q000378:metabolism*; D005786:Gene Expression Regulation; D056945:Hep G2 Cells; D006801:Humans; D006903:Hydroxymethylglutaryl CoA Reductases / Q000378:metabolism*; D057105:Nuclear Receptor Subfamily 4, Group A, Member 1 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000378:metabolism; D011973:Receptors, LDL / Q000378:metabolism*
chemical_list: D057105:Nuclear Receptor Subfamily 4, Group A, Member 1; D034741:RNA, Small Interfering; D011973:Receptors, LDL; D002784:Cholesterol; D006903:Hydroxymethylglutaryl CoA Reductases