TY - JOUR
T1 - Oxygen-dependent differentiation of human keratinocytes
AU - Ngo, Mai A.
AU - Sinitsyna, Nadezda N.
AU - Qin, Qin
AU - Rice, Robert H.
PY - 2007/2
Y1 - 2007/2
N2 - Oxygen is an essential micronutrient. Unlike many internal tissues, human epidermis obtains much of its oxygen supply from the atmosphere (21% oxygen), and it ordinarily experiences higher oxygen levels than internal tissues (estimated≈5%). To test whether epidermal cell growth and differentiation depend upon this higher oxygen level, keratinocyte cultures were studied at 21, 5, and 2% oxygen concentrations. Compared to 21% oxygen, culture in 5% had little effect on growth but led to profound suppression of the differentiation program as assessed by expression of differentiation markers and formation of squames in the superficial layers. Culture in 2% oxygen reduced the growth rate as well as stratification and differentiation. In low-oxygen conditions, the cells exhibited increased colony-forming ability, consistent with a lower proportion of differentiated cells, and increased expression of vascular endothelial growth factor and cyclooxygenase-2. Growth in 21% oxygen led to higher levels of glutathione and expression of oxidant-responsive genes. Electrophoretic mobility supershift assay using an involucrin activator protein 1 (AP1) response element sequence revealed altered binding by proteins of the Jun and Fos families in nuclear extracts. The present data thus demonstrate oxygen-dependent differentiation in human keratinocytes, to which altered utilization of AP1 transcriptional response elements may contribute.
AB - Oxygen is an essential micronutrient. Unlike many internal tissues, human epidermis obtains much of its oxygen supply from the atmosphere (21% oxygen), and it ordinarily experiences higher oxygen levels than internal tissues (estimated≈5%). To test whether epidermal cell growth and differentiation depend upon this higher oxygen level, keratinocyte cultures were studied at 21, 5, and 2% oxygen concentrations. Compared to 21% oxygen, culture in 5% had little effect on growth but led to profound suppression of the differentiation program as assessed by expression of differentiation markers and formation of squames in the superficial layers. Culture in 2% oxygen reduced the growth rate as well as stratification and differentiation. In low-oxygen conditions, the cells exhibited increased colony-forming ability, consistent with a lower proportion of differentiated cells, and increased expression of vascular endothelial growth factor and cyclooxygenase-2. Growth in 21% oxygen led to higher levels of glutathione and expression of oxidant-responsive genes. Electrophoretic mobility supershift assay using an involucrin activator protein 1 (AP1) response element sequence revealed altered binding by proteins of the Jun and Fos families in nuclear extracts. The present data thus demonstrate oxygen-dependent differentiation in human keratinocytes, to which altered utilization of AP1 transcriptional response elements may contribute.
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U2 - 10.1038/sj.jid.5700522
DO - 10.1038/sj.jid.5700522
M3 - Article
C2 - 16977326
AN - SCOPUS:33846250834
VL - 127
SP - 354
EP - 361
JO - Journal of Investigative Dermatology
JF - Journal of Investigative Dermatology
SN - 0022-202X
IS - 2
ER -