Up-Regulation of Drug-Metabolizing Enzyme Genes in Layered Co-Culture of a Human Liver Cell Line and Endothelial Cells
Primary human hepatocytes are used extensively to study drug-metabolizing enzymes such as the cytochrome P450 (CYP) enzymes. However, the activities of these enzymes decrease rapidly during culture. In the present study, using a thermo-responsive culture dish, layered co-culture was achieved by plac...
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| Veröffentlicht in: | Tissue engineering. Part A 2008-11, Vol.14 (11), p.1861-1869 |
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| creator | Ohno, Maki Motojima, Kiyoto Okano, Teruo Taniguchi, Akiyoshi |
| description | Primary human hepatocytes are used extensively to study drug-metabolizing enzymes such as the cytochrome P450 (CYP) enzymes. However, the activities of these enzymes decrease rapidly during culture. In the present study, using a thermo-responsive culture dish, layered co-culture was achieved by placing a bovine pulmonary artery endothelial cell (BPAEC) sheet onto the human hepatoma cell line HepG2. In the BPAEC/HepG2 layered co-culture system, real-time polymerase chain reaction analysis showed that the expression levels of various CYP enzymes were more than 10 times greater 21 days after layering than with a HepG2 monolayer. The expression levels of CYP1B1, CYP2C9, CYP2E1, and CYP3A4 were up-regulated in a time-dependent manner, gradually increasing from day 10 after layering, and continuing to increase until at least day 21. The gene expression levels of the various CYP enzymes were almost identical to that of human liver. These results suggest that our layered co-culture system enhances the function of HepG2 cells and that our BPAEC/HepG2 layered co-culture system can serve as a useful model for the
in vitro
evaluation of CYP regulation. |
| doi_str_mv | 10.1089/ten.tea.2007.0160 |
| format | Article |
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in vitro
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in vitro
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Motojima, Kiyoto ; Okano, Teruo ; Taniguchi, Akiyoshi</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c538t-f59abccb033d0a4148d4eb1b2591e890a50cf698fe1cfaf22fe5b53f724e7cba3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2008</creationdate><topic>Animals</topic><topic>Cattle</topic><topic>Cell culture</topic><topic>Cell Line</topic><topic>Cell Line, Tumor</topic><topic>Coculture Techniques - methods</topic><topic>Cytochrome P-450</topic><topic>Cytochrome P-450 Enzyme System - genetics</topic><topic>Drug metabolism</topic><topic>Endothelial Cells - cytology</topic><topic>Endothelial Cells - metabolism</topic><topic>Enzymes</topic><topic>Gene Expression Regulation, Enzymologic</topic><topic>Genetic aspects</topic><topic>Hepatocytes - cytology</topic><topic>Hepatocytes - metabolism</topic><topic>Humans</topic><topic>Liver cells</topic><topic>Metabolism</topic><topic>Physiological aspects</topic><topic>Reverse Transcriptase Polymerase Chain Reaction</topic><topic>Up-Regulation - genetics</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Ohno, Maki</creatorcontrib><creatorcontrib>Motojima, Kiyoto</creatorcontrib><creatorcontrib>Okano, Teruo</creatorcontrib><creatorcontrib>Taniguchi, Akiyoshi</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>Immunology Abstracts</collection><collection>Neurosciences Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Oncogenes and Growth Factors Abstracts</collection><collection>ProQuest - Health & Medical Complete保健、医学与药学数据库</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Biology Database (Alumni Edition)</collection><collection>Medical Database (Alumni Edition)</collection><collection>Science Database (Alumni Edition)</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Natural Science Collection</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Biological Sciences</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>PML(ProQuest Medical Library)</collection><collection>ProQuest Science Journals</collection><collection>Biological Science Database</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>ProQuest Central Basic</collection><collection>Biotechnology Research Abstracts</collection><collection>Technology Research Database</collection><collection>Engineering Research Database</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>Tissue engineering. Part A</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Ohno, Maki</au><au>Motojima, Kiyoto</au><au>Okano, Teruo</au><au>Taniguchi, Akiyoshi</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Up-Regulation of Drug-Metabolizing Enzyme Genes in Layered Co-Culture of a Human Liver Cell Line and Endothelial Cells</atitle><jtitle>Tissue engineering. Part A</jtitle><addtitle>Tissue Eng Part A</addtitle><date>2008-11-01</date><risdate>2008</risdate><volume>14</volume><issue>11</issue><spage>1861</spage><epage>1869</epage><pages>1861-1869</pages><issn>1937-3341</issn><eissn>1937-335X</eissn><abstract>Primary human hepatocytes are used extensively to study drug-metabolizing enzymes such as the cytochrome P450 (CYP) enzymes. However, the activities of these enzymes decrease rapidly during culture. In the present study, using a thermo-responsive culture dish, layered co-culture was achieved by placing a bovine pulmonary artery endothelial cell (BPAEC) sheet onto the human hepatoma cell line HepG2. In the BPAEC/HepG2 layered co-culture system, real-time polymerase chain reaction analysis showed that the expression levels of various CYP enzymes were more than 10 times greater 21 days after layering than with a HepG2 monolayer. The expression levels of CYP1B1, CYP2C9, CYP2E1, and CYP3A4 were up-regulated in a time-dependent manner, gradually increasing from day 10 after layering, and continuing to increase until at least day 21. The gene expression levels of the various CYP enzymes were almost identical to that of human liver. These results suggest that our layered co-culture system enhances the function of HepG2 cells and that our BPAEC/HepG2 layered co-culture system can serve as a useful model for the
in vitro
evaluation of CYP regulation.</abstract><cop>United States</cop><pub>Mary Ann Liebert, Inc</pub><pmid>18847370</pmid><doi>10.1089/ten.tea.2007.0160</doi><tpages>9</tpages></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1937-3341 |
| ispartof | Tissue engineering. Part A, 2008-11, Vol.14 (11), p.1861-1869 |
| issn | 1937-3341 1937-335X |
| language | eng |
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| source | MEDLINE; Alma/SFX Local Collection |
| subjects | Animals Cattle Cell culture Cell Line Cell Line, Tumor Coculture Techniques - methods Cytochrome P-450 Cytochrome P-450 Enzyme System - genetics Drug metabolism Endothelial Cells - cytology Endothelial Cells - metabolism Enzymes Gene Expression Regulation, Enzymologic Genetic aspects Hepatocytes - cytology Hepatocytes - metabolism Humans Liver cells Metabolism Physiological aspects Reverse Transcriptase Polymerase Chain Reaction Up-Regulation - genetics |
| title | Up-Regulation of Drug-Metabolizing Enzyme Genes in Layered Co-Culture of a Human Liver Cell Line and Endothelial Cells |
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