Role of nuclear factor E2-related factor 2 (Nrf2) in epidermal differentiation.
Nuclear factor E2-related factor 2 (Nrf2) is one of the most important redox-sensitive transcription factors regulating expression of antioxidative genes and cytoprotective enzymes, which constitute the cellular response to oxidative stress and xenobiotic damage. In this study, we investigated the functional role of Nrf2 during normal epidermal keratinocyte (NHEK) differentiation. Immunohistochemical staining showed that Nrf2 is expressed from basal to granular layer of epidermis. When cultured NHEKs were treated with 1.2 mM calcium, Nrf2 expression was increased gradually in protein levels and Nrf2 translocated into the nucleus in a differentiation-dependent manner. When Nrf2 was overexpressed in NHEK by adenoviral transduction, the expression of the NHEK differentiation marker loricrin and keratin 10 was increased and overexpression of Nrf2 also increased the luciferase activity of loricrin in the absence of calcium. These results suggest that Nrf2 helps to promote the differentiation of epidermal keratinocytes.
Department of Dermatology, College of Medicine, Chungnam National University, 55 Munhwa-ro, Daejeon, 301-747, Korea.
Young
Y
Lee
Jung-Min
JM
Shin
Sunhyae
S
Jang
Dae-Kyoung
DK
Choi
Min-Seok
MS
Seo
Hyeong-Rae
HR
Kim
Kyung-Cheol
KC
Sohn
Myung
M
Im
Young-Joon
YJ
Seo
Jeung-Hoon
JH
Lee
Chang-Deok
CD
Kim
D021581:Active Transport, Cell Nucleus; D002118:Calcium / Q000494:pharmacology; D002454:Cell Differentiation; D002478:Cells, Cultured; D000078404:Epidermal Cells; D004817:Epidermis / Q000378:metabolism; D006801:Humans; D053550:Keratin-10 / Q000096:biosynthesis*; D015603:Keratinocytes / Q000166:cytology* / Q000378:metabolism; D008565:Membrane Proteins / Q000096:biosynthesis*; D051267:NF-E2-Related Factor 2 / Q000096:biosynthesis*; D018384:Oxidative Stress
C507493:KRT10 protein, human; D008565:Membrane Proteins; D051267:NF-E2-Related Factor 2; C495635:NFE2L2 protein, human; C064554:loricrin; D053550:Keratin-10; D002118:Calcium