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Ontogeny of the epidermal permeability barrier
M L Williams1, K Hanley, P M Elias
1Dermatology Service, Veterans Affairs Medical Center, San Francisco, California 94121, USA.
Insights
Skin barrier competence develops rapidly in infants, aided by hormonal and environmental factors. Research in fetal rats reveals key regulators of this crucial developmental process.
Area of Science:
- Developmental Biology
- Skin Physiology
- Terrestrial Adaptation
Background:
- A mature skin permeability barrier is essential for survival outside the womb.
- Immature skin in preterm infants leads to significant health complications.
- Infants rapidly develop a competent barrier despite prematurity.
Purpose of the Study:
- To investigate the mechanisms and regulation of skin barrier ontogeny.
- To understand factors influencing the development of skin competence in late gestation.
Main Methods:
- Utilized late-gestation fetal rodents (rats) for study.
- Employed in vitro culture of fetal rat skin.
- Manipulated hormonal and environmental conditions in cultures.
Main Results:
- Barrier competence correlated with epidermal development and stratum corneum lamellar membranes.
- Hormones like glucocorticoids, T3, and estrogen accelerated barrier formation; androgens delayed it.
- Air-liquid interface culture and PPAR/FXR activators accelerated barrier development.
Conclusions:
- Hormonal and environmental factors play critical roles in regulating skin barrier maturation.
- Nuclear receptors and Ca++ are key regulators in late-stage barrier development.
- Findings explain sex-based differences in premature infant outcomes and rapid barrier acquisition.
Abstract:
A competent permeability barrier must be present by the end of gestation to allow for life in a terrestrial environment. Indeed, early preterm infants display serious complications of skin immaturity. Yet, regardless of their degree of prematurity, all infants quickly develop a competent barrier. To learn more about the mechanisms and regulation of barrier ontogeny, we have utilized late-gestation fetal rodents. In 19-21 d fetal rats, we showed that barrier competence is accompanied by both enhanced epidermal development and formation of extracellular lamellar membranes in the stratum corneum. The identical sequence and time-course occurs when fetal rat skin is cultured in a serum-free medium. Glucocorticoids, thyroid hormone (T3), and estrogen accelerate, while androgens delay barrier formation both in utero and in the in vitro system, explaining the poorer outcome of premature males versus females. But neither T3 nor glucocorticoids are absolutely required for barrier development. Lifting fetal skin cultures to an air-medium interface also accelerates barrier formation, explaining the rapid emergence of barrier competence in very premature infants. PPARalpha and FXR activators, which, like T3, heterodimerize with the nuclear receptor, RXR, also accelerate barrier development in vitro. Finally, not only the nuclear receptor family, but also Ca++ could regulate key events late in barrier development.