Research Report
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World J Gastroenterol. Jul 28, 2014; 20(28): 9513-9518
Published online Jul 28, 2014. doi: 10.3748/wjg.v20.i28.9513
Association of caveolin-3 and cholecystokinin A receptor with cholesterol gallstone disease in mice
Guo-Qiang Xu, Cheng-Fu Xu, Hong-Tan Chen, Shan Liu, Xiao-Dong Teng, Gen-Yun Xu, Chao-Hui Yu
Guo-Qiang Xu, Cheng-Fu Xu, Hong-Tan Chen, Shan Liu, Chao-Hui Yu, Department of Gastroenterology, the First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou 310003, Zhejiang Province, China
Xiao-Dong Teng, Department of Pathology, the First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou 310003, Zhejiang Province, China
Gen-Yun Xu, Department of Laboratory Medicine, the First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou 310003, Zhejiang Province, China
Author contributions: Xu GQ, Xu CF, Chen HT and Yu CH designed the research; Xu GQ, Xu CF, Chen HT, Liu S, Teng XD, Xu GY and Yu CH performed the research; Xu GQ, Xu CF, Chen HT and Liu S analyzed the data; and Xu GQ and Xu CF wrote the paper.
Supported by National Natural Science Foundation of China, No. 81070366
Correspondence to: Guo-Qiang Xu, MD, Department of Gastroenterology, the First Affiliated Hospital, College of Medicine, Zhejiang University, 79 Qingchun Road, Hangzhou 310003, Zhejiang Province, China. zyxgq@sina.cn
Telephone: +86-571-87236518 Fax: +86-571-87236611
Received: January 13, 2014
Revised: March 19, 2014
Accepted: April 21, 2014
Published online: July 28, 2014
Abstract

AIM: To investigate the role of caveolin-3 (CAV3) and cholecystokinin A receptor (CCKAR) in cholesterol gallstone disease (CGD).

METHODS: To establish a mouse model of CGD, male C57BL/6 mice were fed with a lithogenic diet containing 1.0% cholic acid, 1.25% cholesterol and 15% fat; a similar control group was given a normal diet. The fresh liver weights and liver-to-body weight ratio were compared between the two groups after one month. Serum lipid profile and bile composition were determined with an autoanalyzer. The Cav3 and Cckar mRNA and CAV3 and CCKAR protein levels in the liver and gallbladder were determined via real-time polymerase chain reaction and Western blot, respectively.

RESULTS: Establishment of the mouse CGD model was verified by the presence of cholesterol gallstones in mice fed the lithogenic diet. Compared with mice maintained on a normal diet, those fed the lithogenic diet had significantly higher mean liver-to-body weight ratio (0.067 ± 0.007 vs 0.039 ± 0.007, P < 0.01), serum total cholesterol (4.22 ± 0.46 mmol/L vs 2.21 ± 0.11 mmol/L, P < 0.001), bile total cholesterol (1.33 ± 0.33 mmol/L vs 0.21 ± 0.11 mmol/L, P < 0.001), and bile phospholipid concentrations (3.55 ± 1.40 mmol/L vs 1.55 ± 0.63 mmol/L, P = 0.04), but lower total bile acid concentrations (726.48 ± 51.83 μmol/L vs 839.83 ± 23.74 μmol/L, P = 0.007). The lithogenic diet was also associated with significantly lower CAV3 in the liver and lower CAV3 and CCKAR in the gallbladder compared with the control mice (all P < 0.05).

CONCLUSION: CAV3 and CCKAR may be involved in cholesterol gallstone disease.

Keywords: Cholesterol gallstone disease, Caveolin-3, Cholecystokinin A receptor, Lithogenic diet, Mechanism

Core tip: Cholesterol gallstone disease (CGD) is one of the most common digestive diseases worldwide, while the mechanisms of this disease are not fully understood. In this study, we established a mouse model of CGD and observed that the formation of gallstones was accompanied by an increase in serum and bile total cholesterol concentrations, while by a decrease in total bile acid concentration in bile. The formation of gallstones was also accompanied by downregulation of hepatic caveolin-3 (CAV3) expression, and downregulation of CAV3 and cholecystokinin A receptor (CCKAR) expression in the gallbladder. Our results suggest that CAV3 and CCKAR may be involved in CGD.