文章基本信息

标题：Deficiency of Capicua disrupts bile acid homeostasis
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作者：Eunjeong Kim ; Sungjun Park ; Nahyun Choi 等
期刊名称：Scientific Reports
电子版ISSN：2045-2322
出版年度：2015
卷号：5
DOI：10.1038/srep08272
出版社：Springer Nature
摘要：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.