| First Author | Kim E | Year | 2015 |
| Journal | Sci Rep | Volume | 5 |
| Pages | 8272 | PubMed ID | 25653040 |
| Mgi Jnum | J:356936 | Mgi Id | MGI:6219831 |
| Doi | 10.1038/srep08272 | Citation | Kim E, et al. (2015) Deficiency of Capicua disrupts bile acid homeostasis. Sci Rep 5:8272 |
| abstractText | 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 (HNF1alpha), CCAAT/enhancer-binding protein beta (C/EBPbeta), forkhead box protein A2 (FOXA2), and retinoid X receptor alpha (RXRalpha), were markedly decreased in Cic-L(-/-) mice. Moreover, induction of tumor necrosis factor alpha (Tnfalpha) expression and decrease in the levels of FOXA2, C/EBPbeta, and RXRalpha 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. |
