期刊
JOURNAL OF STEROID BIOCHEMISTRY AND MOLECULAR BIOLOGY
卷 130, 期 3-5, 页码 147-158出版社
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.jsbmb.2011.06.012
关键词
FXR; PXR; Cholestasis; Nuclear receptor; Liver; Review
资金
- Human Frontier Science Program (HFSP)
- Marie Curie Reintegration grant under 7th Framework Programme of the European Commission
- National Institutes of Health/National Institute of Diabetes and Digestive and Kidney Diseases Nuclear Receptor Signaling Atlas orphan receptor Grant [U19DK62434]
- Environmental Protection Agency Super-fund Program Grant [P42 ES10337]
- Helmsley Charitable Trust
- National Health and Medical Research Council of Australia (NHMRC) project [402493, 512354]
Cholestatic liver disorders encompass hepatobiliary diseases of diverse etiologies characterized by the accumulation of bile acids, bilirubin and cholesterol as the result of impaired secretion of bile. Members of the nuclear receptor (NR) family of ligand-modulated transcription factors are implicated in the adaptive response to cholestasis. NRs coordinately regulate bile acid and phospholipid transporter genes required for hepatobiliary transport, as well as the phases I and II metabolizing enzymes involved in processing of their substrates. In this review we will focus on FXR and PXR, two members of the NR family whose activities are regulated by bile acids. In addition, we also discuss the potential of pharmacological modulators of these receptors as novel therapies for cholestatic disorders. (C) 2011 Elsevier Ltd. All rights reserved.
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