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

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)1970-1978
Number of pages9
JournalProcess Biochemistry
Volume49
Issue number11
DOIs
Publication statusPublished - 2014

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Keywords

  • Adipose-derived stem cells
  • Bone marrow-derived mesenchymal stem cells
  • Cytochrome
  • Human dermal fibroblasts
  • P450 3A4
  • Pregnane
  • X receptor

ASJC Scopus subject areas

  • Biochemistry
  • Applied Microbiology and Biotechnology
  • Bioengineering

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