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Updated: Jun 21, 2026

Isolation and Culture of Primary Mouse Keratinocytes from Neonatal and Adult Mouse Skin
Published on: July 14, 2017
PPARδ activation promotes stratum corneum formation and epidermal permeability barrier development during late
Yan J Jiang1, Grant Barish, Biao Lu
1Department of Veterans Affairs Medical Center, Metabolism Section, Veterans Affairs Medical Center, San Francisco, California 94121, USA. yan.jiang@med.va.gov
Insights
Peroxisome proliferator-activated receptor-delta (PPARdelta) plays a key role in fetal skin development. Activating PPARdelta accelerates stratum corneum (SC) formation and barrier function, crucial for newborn survival.
Area of Science:
- Developmental Biology
- Dermatology
- Molecular Endocrinology
Background:
- Epidermal ontogenesis forms the stratum corneum (SC), essential for post-natal skin barrier function.
- Regulation of epidermal development is not fully understood, though nuclear hormone receptors are implicated.
- Peroxisome proliferator-activated receptor-delta (PPARdelta) is abundant in fetal skin and promotes barrier formation in adults.
Purpose of the Study:
- To investigate the role of PPARdelta in regulating epidermal ontogenesis and permeability barrier development.
- To test the hypothesis that PPARdelta signaling influences fetal skin maturation.
Main Methods:
- Treatment of fetal rat explants with a PPARdelta ligand (GW 610742X).
- Intra-amniotic administration of GW 610742X in rats.
- Analysis of PPARdelta-deficient mice during gestation, assessing SC formation and protein expression.
Main Results:
- PPARdelta activation in rat explants accelerated SC formation, reduced water loss, and enhanced barrier function.
- Intra-amniotic GW 610742X administration similarly promoted SC and barrier development.
- PPARdelta-deficient mice showed delayed SC formation and differentiation protein expression during mid-gestation, with normalization by late gestation.
Conclusions:
- PPARdelta signaling is a critical regulator of fetal epidermal development and stratum corneum formation.
- PPARdelta plays a transient but essential role in establishing the permeability barrier during late gestation.
- Targeting PPARdelta may offer therapeutic potential for developmental skin barrier disorders.
Abstract:
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.
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