Expression profiles of phases 1 and 2 metabolizing enzymes in human skin and the reconstructed skin models Episkin and full thickness model from Episkin.
BACKGROUND
Episkin and full thickness model from Episkin (FTM) are human skin models obtained from in vitro growth of keratinocytes into the five typical layers of the epidermis. FTM is a full thickness reconstructed skin model that also contains fibroblasts seeded in a collagen matrix.


OBJECTIVE
To assess whether enzymes involved in chemical detoxification are expressed in Episkin and FTM and how their levels compare with the human epidermis, dermis and total skin.


METHODS
Quantification of the mRNA expression levels of phases 1 and 2 metabolizing enzymes in cultured Episkin and FTM and human epidermis, dermis and total skin using Realtime PCR.


RESULTS
The data show that the expression profiles of 61 phases 1 and 2 metabolizing enzymes in Episkin, FTM and epidermis are generally similar, with some exceptions. Cytochrome P450-dependent enzymes and flavin monooxygenases are expressed at low levels, while phase 2 metabolizing enzymes are expressed at much higher levels, especially, glutathione-S-transferase P1 (GSTP1) catechol-O-methyl transferase (COMT), steroid sulfotransferase (SULT2B1b), and N-acetyl transferase (NAT5). The present study also identifies the presence of many enzymes involved in cholesterol, arachidonic acid, leukotriene, prostaglandin, eicosatrienoic acids, and vitamin D3 metabolisms.


CONCLUSIONS
The present data strongly suggest that Episkin and FTM represent reliable and valuable in vitro human skin models for studying the function of phases 1 and 2 metabolizing enzymes in xenobiotic metabolisms. They could be used to replace invasive methods or laboratory animals for skin experiments.
Luu-The
Van
V
Oncology, Molecular Endocrinology and Genomic Research Center, Quebec University Hospital Research Center (CRCHUQ) and Laval University, 2705 Laurier Boulevard, Quebec G1 V 4G2, Canada. Van.Luu-The@crchul.ulaval.ca
Duche
Daniel
D
Ferraris
Corinne
C
Meunier
Jean-Roch
JR
Leclaire
Jacques
J
Labrie
Fernand
F
D000293:Adolescent; D000328:Adult; D004817:Epidermis / Q000201:enzymology; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D015603:Keratinocytes / Q000166:cytology / Q000201:enzymology*; D008875:Middle Aged; D012333:RNA, Messenger / Q000378:metabolism*; D012867:Skin / Q000201:enzymology*; D013256:Steroids / Q000378:metabolism; D023822:Tissue Engineering; D015262:Xenobiotics / Q000378:metabolism; D055815:Young Adult
D012333:RNA, Messenger; D013256:Steroids; D015262:Xenobiotics