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Sengupta, A.* ; Lichti, U.F.* ; Carlson, B.A.* ; Cataisson, C.* ; Ryscavage, A.O.* ; Mikulec, C.* ; Conrad, M. ; Fischer, S.M.* ; Hatfield, D.L.* ; Yuspa, S.H.*

Targeted disruption of glutathione peroxidase 4 in mouse skin epithelial cells impairs postnatal hair follicle morphogenesis that is partially rescued through inhibition of COX-2.

J. Invest. Dermatol. 133, 1731-1741 (2013)
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Selenoproteins are essential molecules for the mammalian antioxidant network. We previously demonstrated that targeted loss of all selenoproteins in mouse epidermis disrupted skin and hair development, and caused premature death. In the current study, we targeted specific selenoproteins for epidermal deletion to determine whether similar phenotypes developed. Keratinocyte-specific knockout mice lacking either the glutathione peroxidase 4 (GPx4) or thioredoxin reductase 1 (TR1) gene were generated by cre-lox technology using K14-cre. TR1 knockout mice had a normal phenotype in resting skin, whereas GPx4 loss in the epidermis caused epidermal hyperplasia, dermal inflammatory infiltrate, dysmorphic hair follicles, and alopecia in perinatal mice. Unlike epidermal ablation of all selenoproteins, mice ablated for GPx4 recovered after 5 weeks and had a normal life span. GPx1 and TR1 were upregulated in the skin and keratinocytes of GPx4-knockout mice. GPx4 deletion reduces keratinocyte adhesion in culture and increases lipid peroxidation and cyclooxygenase-2 (COX-2) levels in cultured keratinocytes and whole skin. Feeding a COX-2 inhibitor to nursing mothers partially prevents development of the abnormal skin phenotype in knockout pups. These data link the activity of cutaneous GPx4 to the regulation of COX-2 and hair follicle morphogenesis, and provide insight into the function of individual selenoprotein activity in maintaining cutaneous homeostasis.
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Publication type Article: Journal article
Document type Scientific Article
Keywords Thioredoxin Reductase ; Lipid-peroxidation ; Cholesterol Hydroperoxides ; Cyclooxygenase-2 ; Expression ; Phgpx ; Mice ; Gene ; Carcinogenesis ; Selenium
ISSN (print) / ISBN 0022-202X
e-ISSN 1523-1747
Quellenangaben Volume: 133, Issue: 7, Pages: 1731-1741 Article Number: , Supplement: ,
Publisher Elsevier
Publishing Place New York, NY
Reviewing status Peer reviewed