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Gewählte Publikation:
SHR Neuro Krebs Kardio Lipid Stoffw Microb
Zollner, G; Marschall, HU; Wagner, M; Trauner, M.
Role of nuclear receptors in the adaptive response to bile acids and cholestasis: pathogenetic and therapeutic considerations.
Mol Pharm. 2006; 3(3): 231-251.
Doi: 10.1021/mp060010s
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- Führende Autor*innen der Med Uni Graz
- Trauner Michael
- Zollner Gernot
- Co-Autor*innen der Med Uni Graz
- Wagner Martin
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- Abstract:
- Cholestasis results in intrahepatic accumulation of cytotoxic bile acids which cause liver injury ultimately leading to biliary fibrosis and cirrhosis. Cholestatic liver damage is counteracted by a variety of intrinsic hepatoprotective mechanisms. Such defense mechanisms include repression of hepatic bile acid uptake and de novo bile acid synthesis. Furthermore, phase I and II bile acid detoxification is induced rendering bile acids more hydrophilic. In addition to "orthograde" export via canalicular export systems, these compounds are also excreted via basolateral "alternative" export systems into the systemic circulation followed by renal elimination. Passive glomerular filtration of hydrophilic bile acids, active renal tubular secretion, and repression of tubular bile acid reabsorption facilitate renal bile acid elimination during cholestasis. The underlying molecular mechanisms are mediated mainly at a transcriptional level via a complex network involving nuclear receptors and other transcription factors. So far, the farnesoid X receptor FXR, pregnane X receptor PXR, and vitamin D receptor VDR have been identified as nuclear receptors for bile acids. However, the intrinsic adaptive response to bile acids cannot fully prevent liver injury in cholestasis. Therefore, additional therapeutic strategies such as targeted activation of nuclear receptors are needed to enhance the hepatic defense against toxic bile acids.
- Find related publications in this database (using NLM MeSH Indexing)
- Adaptation, Biological - physiology
- Animals -
- Bile Acids and Salts - metabolism Bile Acids and Salts - secretion
- Bile Ducts, Intrahepatic - metabolism Bile Ducts, Intrahepatic - secretion
- Biological Transport, Active - physiology
- Cholestasis - etiology Cholestasis - therapy
- Enterohepatic Circulation - physiology
- Humans -
- Hydroxylation -
- Kidney - blood supply Kidney - metabolism
- Metabolic Detoxication, Phase II -
- Models, Biological -
- Receptors, Cytoplasmic and Nuclear - metabolism
- Find related publications in this database (Keywords)
- bile acid transport
- bile acid detoxification
- bile acid synthesis
- transcription factors
- nuclear (orphan) receptors