title: CAV1 Prevents Gallbladder Cholesterol Crystallization by Regulating Biosynthesis and Transport of Bile Salts.
abstract: Cholesterol gallstone disease (CGD) is a hepatobiliary disorder which results from a biochemical imbalance in the gallbladder bile. Here we show that loss of CAV1 sensitized mice to lithogenic diet-induced gallbladder cholesterol crystallization, which was associated with dysregulation of several hepatic transporters that efflux cholesterol, phospholipids, and bile salts. The combined effect of increased biliary cholesterol concentration and decreased biliary bile salt secretion in CAV1(-/-) mice led to an increased cholesterol saturation index and the formation of cholesterol crystals. At the signaling level, the ERK/AP-1 pathway seems to mediate the effects of CAV1 on biliary BA homeostasis and might be developed as a therapeutic target for CGD. We propose that CAV1 is an anti-lithogenic factor and that the CAV1(-/-) mice may offer a convenient CGD model to develop therapeutic interventions for this disease. J. Cell. Biochem. 117: 2118-2127, 2016. © 2016 Wiley Periodicals, Inc.
authors.affiliation: Department of Gastroenterology, Zhejiang University School of Medicine, The First Affiliated Hospital, Hangzhou, Zhejiang, 310003, China.
authors.forename: Guoqiang
authors.initials: G
authors.lastname: Xu
authors.affiliation: Department of Nephrology, Zhejiang Province People's Hospital, Hangzhou, Zhejiang, 310014, China.
authors.forename: Yiqiao
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Pathology and Pathophysiology, Zhejiang University School of Medicine, Hangzhou, Zhejiang, 310058, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Jiang
authors.affiliation: Department of Gastroenterology, Zhejiang University School of Medicine, The First Affiliated Hospital, Hangzhou, Zhejiang, 310003, China.
authors.forename: Hongtan
authors.initials: H
authors.lastname: Chen
mesh_terms: D000818:Animals; D001647:Bile Acids and Salts / Q000096:biosynthesis* / Q000235:genetics; D001693:Biological Transport, Active / Q000235:genetics; D051242:Caveolin 1 / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D002784:Cholesterol / Q000235:genetics / Q000378:metabolism*; D005704:Gallbladder / Q000378:metabolism* / Q000473:pathology / Q000502:physiology; D042882:Gallstones / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D020935:MAP Kinase Signaling System; D051379:Mice; D018345:Mice, Knockout
chemical_list: D001647:Bile Acids and Salts; C495541:Cav1 protein, mouse; D051242:Caveolin 1; D002784:Cholesterol
keywords: CAVEOLIN-1; CHOLESTEROL CRYSTALLIZATION; CHOLESTEROL GALLSTONE DISEASE; ERK/AP-1