title: Modulation of cytochrome P450 gene expression in primary hepatocytes on various artificial extracellular matrices.
abstract: We studied effect of artificial extracellular matrices (ECMs), such as collagen I, poly (N-p-vinylbenzyl-4-O-β-D-galactopyranosyl-D-gluconamide)(PVLA) and E-cadherin-IgG Fc (E-cad-Fc) on hepatic metabolism to identify the mechanism of in vivo hepatocellular functional and metabolic integrity. mRNA expression of liver function marker, cytochrome P450 (CYP) and transporter genes in hepatocytes were compared among used ECMs using real-time RT-PCR. mRNA expressions of Cyp2c29 and Cyp2d22 among CYP genes in hepatocytes on PVLA were recovered after 3days due to enhanced liver-specific function by the spheroid formation of hepatocytes whereas mRNA expressions of CYP genes in hepatocytes on collagen and E-cad-Fc drastically decreased with time. mRNA expressions of the Cyp2c29 and Cyp2d22 in hepatocytes on PVLA were more recovered in the presence of epidermal growth factor (EGF) due to the more and bigger spheroid formation of hepatocytes. Multidrug resistance-associated protein 2 (Mrp2) protein was accumulated at intracellular lumen as similar to bile duct in hepatocyte spheroid formed on PVLA, indicating that spheroid formation of hepatocytes is very important for maintaining liver functions.
authors.affiliation: Department of Biomolecular Engineering, Tokyo Institute of Technology, Yokohama 226-8501, Japan.
authors.forename: Tatsuhiko
authors.initials: T
authors.lastname: Adachi
authors.forename: Mitsuaki
authors.initials: M
authors.lastname: Goto
authors.forename: Chong-Su
authors.initials: CS
authors.lastname: Cho
authors.forename: Toshihiro
authors.initials: T
authors.lastname: Akaike
mesh_terms: D000818:Animals; D015820:Cadherins / Q000737:chemistry / Q000378:metabolism; D002478:Cells, Cultured; D024042:Collagen Type I / Q000737:chemistry / Q000378:metabolism; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics*; D004187:Disaccharides / Q000737:chemistry / Q000378:metabolism; D005109:Extracellular Matrix / Q000737:chemistry / Q000378:metabolism*; D005690:Galactose / Q000378:metabolism; D015870:Gene Expression; D022781:Hepatocytes / Q000201:enzymology*; D007141:Immunoglobulin Fc Fragments / Q000737:chemistry / Q000378:metabolism; D007074:Immunoglobulin G / Q000737:chemistry / Q000378:metabolism; D051379:Mice; D000089762:Multidrug Resistance-Associated Protein 2; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics; D018874:Spheroids, Cellular / Q000201:enzymology; D014753:Vinyl Compounds / Q000737:chemistry / Q000378:metabolism
chemical_list: D015820:Cadherins; D024042:Collagen Type I; D003577:Cytochrome P-450 Enzyme System; D004187:Disaccharides; D005690:Galactose; D007141:Immunoglobulin Fc Fragments; D007074:Immunoglobulin G; D000089762:Multidrug Resistance-Associated Protein 2; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D012333:RNA, Messenger; D014753:Vinyl Compounds; C427524:poly-(N-p-vinylbenzyl-O-galactopyranosyl-(1-4)-gluconamide)