Up-regulation of drug-metabolizing enzyme genes in layered co-culture of a human liver cell line and endothelial cells

Maki Ohno, Kiyoto Motojima, Teruo Okano, Akiyoshi Taniguchi*

*この研究の対応する著者

研究成果: Article査読

24 被引用数 (Scopus)

抄録

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.

本文言語English
ページ(範囲)1861-1869
ページ数9
ジャーナルTissue Engineering - Part A.
14
11
DOI
出版ステータスPublished - 2008 11 1
外部発表はい

ASJC Scopus subject areas

  • バイオエンジニアリング
  • 生化学
  • 生体材料
  • 生体医工学

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