title: Differential expression of basolateral and canalicular organic anion transporters during regeneration of rat liver.
abstract: OBJECTIVE
  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 bile acid pool size.
authors.affiliation: Department of Internal Medicine, Aachen University of Technology, Aachen, Germany.
authors.forename: T
authors.initials: T
authors.lastname: Gerloff
authors.forename: A
authors.initials: A
authors.lastname: Geier
authors.forename: B
authors.initials: B
authors.lastname: Stieger
authors.forename: B
authors.initials: B
authors.lastname: Hagenbuch
authors.forename: P J
authors.initials: PJ
authors.lastname: Meier
authors.forename: S
authors.initials: S
authors.lastname: Matern
authors.forename: C
authors.initials: C
authors.lastname: Gartung
mesh_terms: D000818:Animals; D027321:Anion Transport Proteins; D002352:Carrier Proteins / Q000096:biosynthesis*; D002779:Cholestasis / Q000378:metabolism; D006498:Hepatectomy; D008115:Liver Regeneration / Q000502:physiology*; D008297:Male; D024101:Mitochondrial Proteins; D029363:Organic Anion Transporters, Sodium-Dependent; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012269:Ribosomal Proteins / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins; D027981:Symporters
chemical_list: D027321:Anion Transport Proteins; D002352:Carrier Proteins; C093947:MRP2 protein, S cerevisiae; D024101:Mitochondrial Proteins; D029363:Organic Anion Transporters, Sodium-Dependent; D012333:RNA, Messenger; D012269:Ribosomal Proteins; D029701:Saccharomyces cerevisiae Proteins; D027981:Symporters; C071908:sodium-bile acid cotransporter