PPARδ activation promotes stratum corneum formation and epidermal permeability barrier development during late gestation.
The goal of epidermal ontogenesis is to form a stratum corneum (SC), which is required for post-natal permeability barrier function. The regulation of epidermal ontogenesis is poorly understood, but nuclear hormone receptors have been shown to have an important function. As peroxisome proliferator-activated receptor-delta (PPARdelta) is very abundant in fetal epidermis and PPARdelta activation stimulates differentiation and permeability barrier formation in adults, we hypothesized that PPARdelta might regulate epidermal ontogenesis. Treatment of fetal rat explants with the PPARdelta ligand, GW 610742X, accelerates permeability barrier development, evidenced by a decrease in transepidermal water loss and an enhanced outside-in barrier function, attributable to the presence of more mature lamellar membranes in the SC and enhanced expression of loricrin and involucrin. Similarly, the intra-amniotic administration of GW 610742X also accelerates the formation of the SC and permeability barrier development. Finally, in PPARdelta-deficient mice the formation of the SC and the expression of differentiation-related proteins were delayed on days 16.5 and 17.5 of gestation. However, at later stages (day 18.5 and after birth), there were no differences between wild-type- and PPARdelta-deficient mice, indicating only a transient delay in epidermal ontogenesis. These studies show that PPARdelta has a role in SC formation and permeability barrier development.
Jiang
Yan J
YJ
Department of Veterans Affairs Medical Center, Metabolism Section, Veterans Affairs Medical Center, San Francisco, California 94121, USA. yan.jiang@med.va.gov
Barish
Grant
G
Lu
Biao
B
Evans
Ronald M
RM
Crumrine
Debra
D
Schmuth
Matthias
M
Elias
Peter M
PM
Feingold
Kenneth R
KR
D000818:Animals; D002454:Cell Differentiation; D004789:Enzyme Activation; D004817:Epidermis / Q000201:enzymology* / Q000378:metabolism; D005260:Female; D020869:Gene Expression Profiling; D018507:Gene Expression Regulation, Developmental; D051379:Mice; D018345:Mice, Knockout; D047494:PPAR delta / Q000819:agonists / Q000378:metabolism*; D010539:Permeability; D011247:Pregnancy; D011270:Pregnancy, Animal; D051381:Rats; D017207:Rats, Sprague-Dawley; D013844:Thiazoles / Q000494:pharmacology; D013997:Time Factors
C503394:GW 610742; D047494:PPAR delta; D013844:Thiazoles