期刊
MOLECULAR ASPECTS OF MEDICINE
卷 37, 期 -, 页码 57-76出版社
ELSEVIER
DOI: 10.1016/j.mam.2013.12.001
关键词
Nuclear receptors; ATB-binding cassette transporters; Cholestasis
资金
- Austrian Science Foundation [F3517]
- SFB35 project [3509]
Hepatobiliary bile salt (BS) transporters are critical determinants of BS homeostasis controlling intracellular concentrations of BSs and their enterohepatic circulation. Genetic or acquired dysfunction of specific transport systems causes intrahepatic and systemic retention of potentially cytotoxic BSs, which, in high concentrations, may disturb integrity of cell membranes and subcellular organelles resulting in cell death, inflammation and fibrosis. Transcriptional regulation of canalicular BS efflux through bile salt export pump (BSEP), basolateral elimination through organic solute transporters alpha and beta (OST alpha/OST beta) as well as inhibition of hepatocellular BS uptake through basolateral Ne-taurocholate cotransporting polypeptide (NTCP) represent critical steps in protection from hepatocellular BS overload and can be targeted therapeutically. In this article, we review the potential clinical implications of the major BS transporters BSEP, OST alpha/OST beta and NTCP in the pathogenesis of hereditary and acquired cholestatic syndromes, provide an overview on transcriptional control of these transporters by the key regulatory nuclear receptors and discuss the potential therapeutic role of novel transcriptional activators of BS transporters in cholestasis. (C) 2013 The Authors. Published by Elsevier Ltd.
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