mRNA Expression of Liver Nuclear Receptor Genes in Patients with Cholesterol Gallstone Disease_CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Authors：

YANG Shiyong ¹ , WANG Jiancheng ² , HAN Tianquan ² , WANG Xiaoping ¹ , CAI Qu ² , JIANG Zhihong ² , JIANG Zhaoyan ² , CAI Xingxing ² , ZHANG Shengdao ²

1.Department of General Surgery, The First Affiliated Hospital of Nanjing City， Nanjing Medical University, Nanjing 210006， China;;
2.Department of Surgery, Shanghai Institute of Digestive Surgery, Ruijin Hospital, Shanghai Jiaotong University Medical School, Shanghai 200025, ChinaCorresponding Author: WANG Jian-cheng, E-mail: digsurgrj@yahoo.com.cn;

Corresponding author：

Keywords：

Cholesterol gallstone disease; Liver receptor homolog 1; Gene expression

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Objective 　To investigate the mRNA expressions of liver X receptor α (LXRα), farnesoid X receptor (FXR), steroid xenobiotic receptor (SXR) and liver receptor homolog 1 (LRH-1) gene in patients with cholesterol gallstone (CGS) disease in order to elucidate the biomolecular pathogenesis of gallstone formation.
Methods 　Twenty-seven patients with CGS (CGS group) and 10 controls without gallstones (control group) were included in this study. Serum lipid composition (total cholesterol, triglyceride, high density lipoprotein cholesterol, apoprotein B, apoprotein A1), gallstone cholesterol concentration and biliary composition (cholesterol, bile salts, lecithin) were assayed. Biliary total lipid and cholesterol saturation index (CSI) were calculated. mRNA expressions of LRH-1, FXR, SXR and LXRα gene were determined by real-time polymorphism chain reaction.
Results 　Serum high density lipoprotein cholesterol concentration was lower in CGS group than that in control group 〔(0.93±0.05) mmol/L vs (1.33±0.09) mmol/L, P＜0.001〕 and serum apoprotein A1 was also lower in CGS group than that in control group 〔(1.19±0.05) g/L vs (1.36±0.06) g/L, P＜0.05〕. There were no differences in serum total cholesterol, triglyceride and apoprotein B between two groups (P gt;0.05). CSI was higher in CGS group than that in control group (1.17±0.02 vs 0.79±0.10), P＜0.001. Biliary cholesterol was also higher in CGS group than that in control group 〔(7.96±0.39) mol% vs (5.26±0.89) mol%, P＜0.01〕, while biliary total lipid was lower in CGS group than that in control group 〔(104.72±10.51) g/L vs (154.24±14.20) g/L, P＜0.05〕. There were no differences in bile salts and lecithin between two groups (P gt;0.05). Expression of LRH-1 gene was higher in CGS group than that in control group (14.18±1.80 vs 7.22±2.22), the difference was statistically significant (P＜0.05). There were no differences in mRNA expressions of LXRα, FXR and SXR gene between two groups (P gt;0.05).
Conclusion 　CGS disease may be related to increased expression of LRH-1 gene.

Citation： YANG Shiyong,WANG Jiancheng,HAN Tianquan,WANG Xiaoping,CAI Qu,JIANG Zhihong,JIANG Zhaoyan,CAI Xingxing,ZHANG Shengdao. mRNA Expression of Liver Nuclear Receptor Genes in Patients with Cholesterol Gallstone Disease. CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY, 2008, 15(10): 751-755. doi: Copy

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20.	Luo Y, Liang CP, Tall AR. The orphan nuclear receptor LRH-1 potentiates the sterol-mediated induction of the human CETP gene by liver X receptor [Ｊ]. J Biol Chem, 2001; 276(27)∶24767.

1. 　McKenna NJ, O’Malley BW. Combinatorial control of gene expression by nuclear receptors and coregulators [Ｊ]. Cell, 2002; 108(4)∶465.
2. 　Lammert F, Carey MC, Paigen B. Chromosomal organization of candidate genes involved in cholesterol gallstone formation： a murine gallstone map [Ｊ]. Gastroenterology, 2001; 120(1)∶221.
3. 　Fayard E, Auwerx J, Schoonjans K. LRH-1: an orphan nuclear receptor involved in development, metabolism and steroidogenesis [Ｊ]. Trends Cell Biol, 2004; 14(5)∶250.
4. 　Eloranta JJ, Kullak-Ublick GA. Coordinate transcriptional regulation of bile acid homeostasis and drug metabolism [Ｊ]. Arch Biochem Biophys, 2005; 433(2)∶397.
5. 　Liu Y, Binz J, Numerick MJ, et al. Hepatoprotection by the farnesoid X receptor agonist GW4064 in rat models of intra- and extrahepatic cholestasis [Ｊ]. J Clin Invest, 2003; 112(11)∶16786　Wang DQ, Afdhal NH. Genetic analysis of cholesterol gallstone formation： searching for Lith (gallstone) genes [Ｊ]. Curr Gastroenterol Rep, 2004; 6(2)∶140.
6. 　孔凡民，隋春阳，李航宇，等. 胆囊胆固醇结石与肝细胞胆管膜上转运子BSEP、MRP2和MDR3关系的研究 [Ｊ]. 中国普外基础与临床杂志, 2006; 13(3)∶314.
7. 　刘君，龙厚勇，明晗昕，等. 肝细胞MDR1基因表达与胆囊胆固醇结石相关性研究 [Ｊ]. 中国普外基础与临床杂志, 2005; 12(4)∶346.
8. 　汤文浩, 韩天权, 张圣道. 测定胆汁胆固醇和磷脂的简捷方法 [Ｊ]. 上海医学检验杂志, 1994; 9(2)∶122.
9. 　Carey MC. Critical tables for calculating the cholesterol saturation of native bile [Ｊ]. J Lipid Res, 1978; 19(8)∶945.
10. 　傅培彬，张圣道，戴坤扬，等. 以胆石剖面结构及化学成分为基础的胆石分类法 [Ｊ]. 中华外科杂志, 1984, 22(4)∶258.
11. 　Escriva H, Delaunay F, Laudet V. Ligand binding and nuclear receptor evolution [Ｊ]. Bioessays, 2000; 22(8)∶717.
12. 　Moschetta A, Bookout AL, Mangelsdorf DJ. Prevention of cholesterol gallstone disease by FXR agonists in a mouse model [Ｊ]. Nat Med, 2004; 10(12)∶1352.
13. 　Kosters A, Jirsa M, Groen AK. Genetic background of cholesterol gallstone disease [Ｊ]. Biochim Biophys Acta, 2003; 1637(1)∶1.
14. 　Moschetta A, vanBerge-Henegouwen GP, Portincasa P, et al. Cholesterol crystallization in model biles： effects of bile salt and phospholipid species composition [Ｊ]. J Lipid Res, 2001; 42(8)∶1273.
15. 　蒋兆彦，韩天权，所广军，等. 胆固醇结石病人肝脏胆小管侧膜ATP基因表达差异的研究 [Ｊ]. 外科理论与实践, 2005; 10(1)∶61.
16. 　Bertolotti M, Gabbi C, Anzivino C, et al. Decreased hepatic expression of PPAR-gamma coactivator-1 in cholesterol cholelithiasis [Ｊ]. Eur J Clin Invest, 2006; 36(3)∶170.
17. 　Staudinger JL, Goodwin B, Jones SA, et al. The nuclear receptor PXR is a lithocholic acid sensor that protects against liver toxicity [Ｊ]. Proc Natl Acad Sci USA, 2001; 98(6)∶3369.
18. 　Schoonjans K, Annicotte JS, Huby T, et al. Liver receptor homolog 1 controls the expression of the scavenger receptor class B type Ⅰ [Ｊ]. EMBO Rep, 2002; 3(12)∶1181.
19. 　Freeman LA, Kennedy A, Wu J, et al. The orphan nuclear receptor LRH-1 activates the ABCG5/ABCG8 intergenic promoter [Ｊ]. J Lipid Res, 2004; 45(7)∶1197.
20. 　Luo Y, Liang CP, Tall AR. The orphan nuclear receptor LRH-1 potentiates the sterol-mediated induction of the human CETP gene by liver X receptor [Ｊ]. J Biol Chem, 2001; 276(27)∶24767.

CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

mRNA Expression of Liver Nuclear Receptor Genes in Patients with Cholesterol Gallstone Disease

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