Expressions of hepatobiliary organic anion transporters and bilirubin-conjugating enzyme in differentiating embryonic stem cells

Biochem Biophys Res Commun. 2003 Sep 19;309(2):324-30. doi: 10.1016/j.bbrc.2003.07.005.

Abstract

Mouse embryonic stem (ES) cells are clonal cell lines derived from the inner cell mass of developing blastocysts and have multi-lineage differentiation ability. We previously reported that ES cells can be made to differentiate into hepatocytes possessing high metabolic activities by transfection of hepatocyte nuclear factor-3beta (HNF-3beta). In the present study, we investigated the expression of hepatobiliary organic anion transporters and bilirubin uridine diphosphate glucuronosyltransferase (ugt1a1) in undifferentiated and differentiating HNF-3beta-transfected ES (HNF-3beta-ES) cells. The expression of organic anion transporting polypeptide 1 (oatp1), multidrug resistance-associated protein 1 (mrp1), mrp2, mrp3, and ugt1a1 was not seen in the undifferentiated HNF-3beta-ES cells by RT-PCR, whereas all were expressed in differentiating HNF-3beta-ES cells. Protein expression for oatp1, mrp1, mrp2, mrp3, and ugt1a1 was also observed in the differentiating HNF-3beta-ES cells by Western blotting. An immunofluorescence examination revealed that oatp1 was co-located with desmoplakin, a marker for the basolateral (sinusoidal) membrane, and mrp2 was co-localized with CD26, a marker for the apical (canalicular) membrane, though they were both expressed throughout most of the cell membranes.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Differentiation
  • Cell Line
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism*
  • Gene Expression Regulation, Developmental
  • Glucuronosyltransferase / biosynthesis*
  • Glucuronosyltransferase / genetics
  • Hepatocyte Nuclear Factor 3-beta
  • Hepatocytes / cytology
  • Hepatocytes / metabolism*
  • Mice / embryology
  • Mice / genetics
  • Multidrug Resistance-Associated Proteins / biosynthesis*
  • Multidrug Resistance-Associated Proteins / genetics
  • Nuclear Proteins / genetics
  • Nuclear Proteins / metabolism*
  • Organic Anion Transporters / biosynthesis*
  • Organic Anion Transporters / genetics
  • Stem Cells / cytology
  • Stem Cells / metabolism*
  • Transcription Factors*
  • Transfection / methods

Substances

  • DNA-Binding Proteins
  • Foxa2 protein, mouse
  • Multidrug Resistance-Associated Proteins
  • Nuclear Proteins
  • Organic Anion Transporters
  • Transcription Factors
  • Hepatocyte Nuclear Factor 3-beta
  • UGT1A1 enzyme
  • Glucuronosyltransferase