Deficiency of Capicua disrupts bile acid homeostasis

Eunjeong Kim, Sungjun Park, Nahyun Choi, Jieon Lee, Jeehyun Yoe, Soeun Kim, Hoe Yune Jung, Kyong Tai Kim, Hyojin Kang, John D. Fryer, Huda Y. Zoghbi, Daehee Hwang, Yoontae Lee

Research output: Contribution to journalArticle

12 Citations (Scopus)

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 (HNF1α), CCAAT/enhancer-binding protein beta (C/EBPβ), forkhead box protein A2 (FOXA2), and retinoid X receptor alpha (RXRα), were markedly decreased in Cic-L-/- mice. Moreover, induction of tumor necrosis factor alpha (TNFα) expression and decrease in the levels of FOXA2, C/EBPβ, and RXRα 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.

Original languageEnglish (US)
Article number8272
JournalScientific Reports
Volume5
DOIs
StatePublished - Feb 5 2015

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Bile Acids and Salts
Homeostasis
Retinoid X Receptor alpha
Liver
CCAAT-Enhancer-Binding Protein-beta
Hepatocyte Nuclear Factor 3-beta
Hepatocyte Nuclear Factor 1
Cytokines
Spinocerebellar Ataxias
Cholestasis
Gallbladder
Bile
Genes
Liver Diseases
Mammals
Chronic Disease
Tumor Necrosis Factor-alpha
Inflammation
Serum
Pharmaceutical Preparations

ASJC Scopus subject areas

  • General

Cite this

Kim, E., Park, S., Choi, N., Lee, J., Yoe, J., Kim, S., ... Lee, Y. (2015). Deficiency of Capicua disrupts bile acid homeostasis. Scientific Reports, 5, [8272]. https://doi.org/10.1038/srep08272

Deficiency of Capicua disrupts bile acid homeostasis. / Kim, Eunjeong; Park, Sungjun; Choi, Nahyun; Lee, Jieon; Yoe, Jeehyun; Kim, Soeun; Jung, Hoe Yune; Kim, Kyong Tai; Kang, Hyojin; Fryer, John D.; Zoghbi, Huda Y.; Hwang, Daehee; Lee, Yoontae.

In: Scientific Reports, Vol. 5, 8272, 05.02.2015.

Research output: Contribution to journalArticle

Kim, E, Park, S, Choi, N, Lee, J, Yoe, J, Kim, S, Jung, HY, Kim, KT, Kang, H, Fryer, JD, Zoghbi, HY, Hwang, D & Lee, Y 2015, 'Deficiency of Capicua disrupts bile acid homeostasis', Scientific Reports, vol. 5, 8272. https://doi.org/10.1038/srep08272
Kim E, Park S, Choi N, Lee J, Yoe J, Kim S et al. Deficiency of Capicua disrupts bile acid homeostasis. Scientific Reports. 2015 Feb 5;5. 8272. https://doi.org/10.1038/srep08272
Kim, Eunjeong ; Park, Sungjun ; Choi, Nahyun ; Lee, Jieon ; Yoe, Jeehyun ; Kim, Soeun ; Jung, Hoe Yune ; Kim, Kyong Tai ; Kang, Hyojin ; Fryer, John D. ; Zoghbi, Huda Y. ; Hwang, Daehee ; Lee, Yoontae. / Deficiency of Capicua disrupts bile acid homeostasis. In: Scientific Reports. 2015 ; Vol. 5.
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