Higher expression of cytochrome P450 3A4 in human mesenchymal and adipose-derived stem cells than in dermal fibroblasts: With emphasis on the correlation with basal pregnane X receptor expression

Tsai Shin Chiang, Kai Chiang Yang, Yao Ming Wu, Hong Shiee Lai, Ching Chuan Jiang, Ling Ling Chiou, Kuang Lun Lee, Guan Tarn Huang, Hsuan Shu Lee

研究成果: 雜誌貢獻文章同行評審

1 引文 斯高帕斯(Scopus)

摘要

Among the cytochrome P 450 (CYP) enzymes, CYP3A4 is most abundantly existed and metabolizes most of the drugs. We have shown human dermal fibroblasts (HDFs) express low levels of CYPs, but could be engineered to express much higher levels to be used as drug metabolism prediction. To seek better cell source for engineering, the basal mRNA expression and enzyme activities of CYP3A4 in HDFs (n = 5), bone marrow-derived mesenchymal stem cells (BMMSCs, n = 7), and adipose-derived stem cells (ADSCs, n = 3) were compared. The basal CYP3A4 expression and activity in BMMSCs and ADSCs were significantly higher than in HDFs. However, the coefficient of variation of CYP3A4 expression was very high in each cell type. Comparing the expression levels of 4 regulators glucocorticoid receptor, pregnane X receptor (PXR), hepatocyte nuclear factor 4α, and hydrocarbon receptor nuclear translocator in the total 15 cell samples, we found the only basal PXR expression was significantly correlated with CYP3A4 expression. The gender and age of patients were not significant determinants in the expressions of PXR and CYP3A4. In conclusion, BMMSCs and ADSCs expressed higher levels of CYP3A4 than HDFs and the expression of CYP3A4 might be mainly determined by basal PXR expression.
原文英語
頁(從 - 到)1983-1989
頁數7
期刊Process Biochemistry
49
發行號11
DOIs
出版狀態已發佈 - 十一月 2014

ASJC Scopus subject areas

  • 生物工程
  • 生物化學
  • 應用微生物與生物技術

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