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Cited 11 time in webofscience Cited 12 time in scopus
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Deficiency of Capicua disrupts bile acid homeostasis

Title
Deficiency of Capicua disrupts bile acid homeostasis
Authors
Kim, EPark, SChoi, NLee, JYoe, JKim, SJung, HYKIM, KYONG TAIKang, HFryer, JDZoghbi, HYHwang, DLEE, YOONTAE
Date Issued
Feb-2015
Publisher
nature publishing group
Abstract
Capicua (CIC) has been implicated in pathogenesis of spinocerebellar ataxia type 1 and cancer in mammals; however, the in vivo physiological functions of CIC remain largely unknown. Here we show that Cic hypomorphic (Cic-L-/-) mice have impaired bile acid (BA) homeostasis associated with induction of proinflammatory cytokines. We discovered that several drug metabolism and BA transporter genes were down-regulated in Cic-L-/- liver, and that BA was increased in the liver and serum whereas bile was decreased within the gallbladder of Cic-L-/- mice. We also found that levels of proinflammatory cytokine genes were up-regulated in Cic-L-/- liver. Consistent with this finding, levels of hepatic transcriptional regulators, such as hepatic nuclear factor 1 alpha (HNF1 alpha), CCAAT/enhancer-binding protein beta (C/EBP beta), forkhead box protein A2 (FOXA2), and retinoid X receptor alpha (RXR alpha), were markedly decreased in Cic-L-/- mice. Moreover, induction of tumor necrosis factor alpha (Tnf alpha) expression and decrease in the levels of FOXA2, C/EBP beta, and RXRa were found in Cic-L-/- liver before BA was accumulated, suggesting that inflammation might be the cause for the cholestasis in Cic-L-/- mice. Our findings indicate that CIC is a critical regulator of BA homeostasis, and that its dysfunction might be associated with chronic liver disease and metabolic disorders.
URI
http://oasis.postech.ac.kr/handle/2014.oak/13061
ISSN
2045-2322
Article Type
Article
Citation
Scientific Reports, vol. 5, 2015-02
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 KIM, KYONG TAI
Div of Integrative Biosci & Biotech
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