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Differential expression of basolateral and canalicular organic anion transporters during regeneration of rat liver

Gerloff, T. and Geier, A. and Stieger, B. and Hagenbuch, B. and Meier, P. J. and Matern, S. and Gartung, C.. (1999) Differential expression of basolateral and canalicular organic anion transporters during regeneration of rat liver. Gastroenterology, Vol. 117, H. 6. S. 1408-1415.

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Official URL: http://edoc.unibas.ch/dok/A5261685

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Abstract

BACKGROUND & AIMS: Liver regeneration in response to various forms of injury or surgical resection is a complex process resulting in restoration of the original liver mass and maintenance of liver-specific functions such as bile formation. However, liver regeneration is frequently associated with cholestasis, whose molecular pathogenesis remains unknown. METHODS: To study the molecular mechanisms leading to cholestasis, expression of all major hepatic organic anion transporters contributing to bile formation was determined for up to 2 weeks in rats after 70% partial hepatectomy. RESULTS: Inversely related to serum bile acid levels, basolateral transporters including the sodium-taurocholate cotransporter (Ntcp) and the organic anion transporting polypeptides Oatp1 and Oatp2 were markedly down-regulated at both protein and steady-state mRNA levels by 50%-60% of controls (P > 0.05) during early replicative stages of regeneration (12 hours to 2 days) with a slightly delayed time course for Oatp2. Expression of all basolateral transporters returned to control values between 4 and 4 days after partial hepatectomy. In contrast, protein and mRNA expression of both the canalicular ATP-dependent bile salt export pump (Bsep) and the multiorganic anion transporter Mrp2 remained unchanged or were slightly increased during liver regeneration, but also returned to control values 7-14 days after partial hepatectomy. CONCLUSIONS: The data suggest a differential regulation of basolateral and canalicular organic anion transporters in the regenerating liver. Unaltered expression of Bsep and Mrp2 provides a potential molecular mechanism for regenerating liver cells to maintain or even increase bile secretion expressed per weight of remaining liver. However, down-regulation of basolateral organic anion transporters might protect replicating liver cells by diminishing uptake of potentially hepatotoxic bile salts, because the remaining liver initially cannot cope with the original b
Faculties and Departments:11 Rektorat und Verwaltung > Vizerektorat Forschung
UniBasel Contributors:Meier-Abt, Peter J.
Item Type:Article, refereed
Bibsysno:Link to catalogue
Publisher:Saunders
ISSN:0016-5085
Note:Publication type according to Uni Basel Research Database: Journal article
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Last Modified:22 Mar 2012 14:23
Deposited On:22 Mar 2012 13:35

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