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SHR Neuro Krebs Kardio Lipid Stoffw Microb
Geier, A; Wagner, M; Dietrich, CG; Trauner, M.
Principles of hepatic organic anion transporter regulation during cholestasis, inflammation and liver regeneration.
Biochim Biophys Acta. 2007; 1773(3): 283-308.
Doi: 10.1016/j.bbamcr.2006.04.014
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- Co-Autor*innen der Med Uni Graz
- Trauner Michael
- Wagner Martin
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- Abstract:
- Hepatic uptake and biliary excretion of organic anions (e.g., bile acids and bilirubin) is mediated by hepatobiliary transport systems. Defects in transporter expression and function can cause or maintain cholestasis and jaundice. Recruitment of alternative export transporters in coordination with phase I and II detoxifying pathways provides alternative pathways to counteract accumulation of potentially toxic biliary constituents in cholestasis. The genes encoding for organic anion uptake (NTCP, OATPs), canalicular export (BSEP, MRP2) and alternative basolateral export (MRP3, MRP4) in liver are regulated by a complex interacting network of hepatocyte nuclear factors (HNF1, 3, 4) and nuclear (orphan) receptors (e.g., FXR, PXR, CAR, RAR, LRH-1, SHP, GR). Bile acids, proinflammatory cytokines, hormones and drugs mediate causative and adaptive transporter changes at a transcriptional level by interacting with these nuclear factors and receptors. Unraveling the underlying regulatory mechanisms may therefore not only allow a better understanding of the molecular pathophysiology of cholestatic liver diseases but should also identify potential pharmacological strategies targeting these regulatory networks. This review is focused on general principles of transcriptional basolateral and canalicular transporter regulation in inflammation-induced cholestasis, ethinylestradiol- and pregnancy-associated cholestasis, obstructive cholestasis and liver regeneration. Moreover, the potential therapeutic role of nuclear receptor agonists for the management of liver diseases is highlighted.
- Find related publications in this database (using NLM MeSH Indexing)
- Animals -
- Cholestasis - genetics Cholestasis - metabolism Cholestasis - pathology
- Gene Expression Regulation -
- Humans -
- Inflammation - genetics Inflammation - metabolism Inflammation - pathology
- Liver - metabolism Liver - pathology
- Liver Regeneration -
- Organic Anion Transporters - genetics Organic Anion Transporters - metabolism
- Find related publications in this database (Keywords)
- cholestasis
- liver regeneration
- endotoxin
- cytokines
- nuclear (orphan) receptor
- hepatocyte-enriched transcription factor