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Deficiency of Capicua disrupts bile acid homeostasis

Title
Deficiency of Capicua disrupts bile acid homeostasis
Authors
Kim, EunjeongPark, SungjunChoi, NahyunLee, JieonYoe, JeehyunKim, SoeunJung, Hoe-YuneKim, Kyong-TaiKang, HyojinFryer, John D.Zoghbi, Huda Y.Hwang, DaeheeLee, Yoontae
DGIST Authors
Hwang, Daehee
Issue Date
2015-02
Citation
Scientific Reports, 5
Type
Article
Article Type
Article
ISSN
2045-2322
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://hdl.handle.net/20.500.11750/2936
DOI
10.1038/srep08272
Publisher
Nature Publishing Group
Related Researcher
  • Author Hwang, Daehee Systems Biology and Medicine Lab
  • Research Interests Multilayered spatiotemporal networks; Regulatory motifs or pathways; Metabolite-protein networks; Network stochasticity; Proteomics and informatics
Files:
Collection:
Department of New BiologySystems Biology and Medicine Lab1. Journal Articles


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