Deficiency of Capicua disrupts bile acid homeostasis
SCIE
SCOPUS
- Title
- Deficiency of Capicua disrupts bile acid homeostasis
- Authors
- Kim, E; Park, S; Choi, N; Lee, J; Yoe, J; Kim, S; Jung, HY; KIM, KYONG TAI; Kang, H; Fryer, JD; Zoghbi, HY; Hwang, D; LEE, YOONTAE
- Date Issued
- 2015-02-05
- 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
- https://oasis.postech.ac.kr/handle/2014.oak/13061
- DOI
- 10.1038/SREP08272
- ISSN
- 2045-2322
- Article Type
- Article
- Citation
- Scientific Reports, vol. 5, 2015-02-05
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