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

• Published in: Biochemical and biophysical research communications Vol. 309; no. 2; pp. 324 - 330
• Main Authors: Tanaka, Yuji, Yoshikawa, Masahide, Kobayashi, Yoshinao, Kuroda, Makoto, Kaito, Masahiko, Shiroi, Akira, Yamao, Jun-ichi, Fukui, Hiroshi, Ishizaka, Shigeaki, Adachi, Yukihiko
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 19.09.2003
• Subjects: Animals; Cell Differentiation; Cell Line; DNA-Binding Proteins - genetics; DNA-Binding Proteins - metabolism; Embryonic stem cell; Gene Expression Regulation, Developmental; Glucuronosyltransferase - biosynthesis; Glucuronosyltransferase - genetics; Hepatocyte Nuclear Factor 3-beta; Hepatocytes - cytology; Hepatocytes - metabolism; Mice - embryology; Mice - genetics; Mrp2; Multidrug Resistance-Associated Proteins - biosynthesis; Multidrug Resistance-Associated Proteins - genetics; Nuclear Proteins - genetics; Nuclear Proteins - metabolism; Oatp1; Organic anion; Organic Anion Transporters - biosynthesis; Organic Anion Transporters - genetics; Stem Cells - cytology; Stem Cells - metabolism; Transcription Factors; Transfection - methods; Transporter; ugt1a1; Embryonic stem cell; ugt1a1; Organic anion; Mrp2; Oatp1; Transporter
• ISSN: 0006-291X; 1090-2104
• DOI: 10.1016/j.bbrc.2003.07.005

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-3β (HNF-3β). In the present study, we investigated the expression of hepatobiliary organic anion transporters and bilirubin uridine diphosphate glucuronosyltransferase (ugt1a1) in undifferentiated and differentiating HNF-3β-transfected ES (HNF-3β-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-3β-ES cells by RT-PCR, whereas all were expressed in differentiating HNF-3β-ES cells. Protein expression for oatp1, mrp1, mrp2, mrp3, and ugt1a1 was also observed in the differentiating HNF-3β-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.