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Deficiency of Capicua disrupts bile acid homeostasis

Deficiency of Capicua disrupts bile acid homeostasis
Kim, E[Kim, Eunjeong]Park, S[Park, Sungjun]Choi, N[Choi, Nahyun]Lee, J[Lee, Jieon]Yoe, J[Yoe, Jeehyun]Kim, S[Kim, Soeun]Jung, HY[Jung, Hoe-Yune]Kim, KT[Kim, Kyong-Tai]Kang, H[Kang, Hyojin]Fryer, JD[Fryer, John D.]Zoghbi, HY[Zoghbi, Huda Y.]Hwang, D[Hwang, Daehee]Lee, Y[Lee, Yoontae]
DGIST Authors
Hwang, D[Hwang, Daehee]
Issue Date
Scientific Reports, 5
Article Type
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.
Nature Publishing Group
Related Researcher
  • Author Hwang, Dae Hee Systems Biology and Medicine Lab
  • Research Interests Multilayered spatiotemporal networks; Regulatory motifs or pathways; Metabolite-protein networks; Network stochasticity; Proteomics and informatics
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Department of New BiologySystems Biology and Medicine Lab1. Journal Articles

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