ABSTRACT
Objective:To investigate the expressions of liver receptor homolog 1 (LRH-1) and scavenger receptor B type Ⅰ (SRBI) gene in cholesterol gallstone (CGS) mice.Methods:Forty C57BL/6 mice,20 with cholesterol gallstone (GS)and 20 controls without gallstones (GSF) were enrolled in this study.mRNA and protein expression of LRH-1 and SRBI genes were determined by RT-PCR and Western blot.Results:Gallbladder walls of GS mice were thicker with increased stromal granulocyte infiltration.The expression levels of LRH-1 genes were significantly higher in GS mice than in controls(P＜0.01).The expression levels of SRBI genes were also significantly higher in GS mice than in controls(P＜0.01).Conclusion:The increased expression of LRH-1 and SRBI gene may be related to GS disease.
ABSTRACT
Objective:To investigate the expressions of liver receptor homolog 1 (LRH-1) and scavenger receptor B type Ⅰ (SRBI) gene in cholesterol gallstone (CGS) mice.Methods:Forty C57BL/6 mice,20 with cholesterol gallstone (GS)and 20 controls without gallstones (GSF) were enrolled in this study.mRNA and protein expression of LRH-1 and SRBI genes were determined by RT-PCR and Western blot.Results:Gallbladder walls of GS mice were thicker with increased stromal granulocyte infiltration.The expression levels of LRH-1 genes were significantly higher in GS mice than in controls(P＜0.01).The expression levels of SRBI genes were also significantly higher in GS mice than in controls(P＜0.01).Conclusion:The increased expression of LRH-1 and SRBI gene may be related to GS disease.
ABSTRACT
BACKGROUND: Expression of hepatic cholesterol 7alpha-hydroxylase (CYP7A1) is negatively regulated by orphan nuclear receptor small heterodimer partner (SHP). In this study, we aimed to find whether thyroid hormone regulates SHP expression by modulating the transcriptional activities of liver receptor homolog-1 (LRH-1). METHODS: We injected thyroid hormone (triiodothyronine, T3) to C57BL/6J wild type. RNA was isolated from mouse liver and used for microarray analysis and quantitative real-time polymerase chain reaction (PCR). Human hepatoma cell and primary hepatocytes from mouse liver were used to confirm the effect of T3 in vitro. Promoter assay and electrophoretic mobility-shift assay (EMSA) were also performed using human hepatoma cell line RESULTS: Initial microarray results indicated that SHP expression is markedly decreased in livers of T3 treated mice. We confirmed that T3 repressed SHP expression in the liver of mice as well as in mouse primary hepatocytes and human hepatoma cells by real-time PCR analysis. LRH-1 increased the promoter activity of SHP; however, this increased activity was markedly decreased after thyroid hormone receptor beta/retinoid X receptor alpha/T3 administration. EMSA revealed that T3 inhibits specific LRH-1 DNA binding. CONCLUSION: We found that thyroid hormone regulates the expression of SHP mRNA through interference with the transcription factor, LRH-1.
Subject(s)
Animals , Child , Humans , Mice , Bile Acids and Salts , Carcinoma, Hepatocellular , Cell Line , Child, Orphaned , Cholesterol , Cholesterol 7-alpha-Hydroxylase , DNA , Hepatocytes , Liver , Microarray Analysis , Real-Time Polymerase Chain Reaction , Receptors, Thyroid Hormone , RNA , RNA, Messenger , Thyroid Gland , Thyroid Hormones , Transcription FactorsABSTRACT
Objective To investigate the mRNA expression of liver receptor homolog 1 (LRH-1) gene in patients with cholesterol gallstone disease so that to elucidate the biomolecular pathogenesis of gallstone for- mation.Methods Twenty-seven patients with cholesterol gallstone (CGS) and 14 controls were included in this study.Biliary composition was assayed and mRNA expression of hepatic LRH 1 gene was determined by real time polymorphism chain reaction.Results In CGS patients,expression of LRH-1 was significantly higher than that in controls (14.18?9.37 vs 7.86?6.19,P＜0.05),and cholesterol of bile was oversaturated (1.17?0.27).Conclusion The formation of CGS may be related to increased expression of hepatic LRH-1 gene.