Glucocorticoids accelerate fetal maturation of the epidermal permeability barrier in the rat.

Aszterbaum, Michelle; Feingold, Kenneth R.; Menon, Gopinathan K.; Williams, Mary L.

doi:10.1172/jci116509

Cited by 73 publications

(47 citation statements)

References 46 publications

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“…For example, studies in rodents have demonstrated that corticosteroids accelerate epidermal barrier acquisition, which may contribute to their beneficial effect on treating inflammatory disorders, independent of their immunosuppressive effects (11,59). Previous studies on the role of connexins have demonstrated that downregulation of Cx43, either through genetic deletion or antisense treatment, resulted in accelerated wound closure (60,61).…”

Section: Discussionmentioning

confidence: 99%

Connexin 26 regulates epidermal barrier and wound remodeling and promotes psoriasiform response

Djalilian¹

2006

Journal of Clinical Investigation

115

107

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Inflammatory skin disorders result in significant epidermal changes, including keratinocyte hyperproliferation, incomplete differentiation, and impaired barrier. Here we test whether, conversely, an impaired epidermal barrier can promote an inflammatory response. Mice lacking the transcription factor Kruppel-like factor 4 (Klf4) have a severe defect in epidermal barrier acquisition. Transcription profiling of Klf4 -/-newborn skin revealed similar changes in gene expression to involved psoriatic plaques, including a significant upregulation of the gap junction protein connexin 26 (Cx26). Ectopic expression of Cx26 from the epidermis-specific involucrin (INV) promoter (INV-Cx26) demonstrated that downregulation of Cx26 is required for barrier acquisition during development. In juvenile and adult mice, persistent Cx26 expression kept wounded epidermis in a hyperproliferative state, blocked the transition to remodeling, and led to an infiltration of immune cells. Mechanistically, ectopic expression of Cx26 in keratinocytes resulted in increased ATP release, which delayed epidermal barrier recovery and promoted an inflammatory response in resident immune cells. These results provide a molecular link between barrier acquisition in utero and epidermal remodeling after wounding. More generally, these studies suggest that the most effective treatments for inflammatory skin disorders might concomitantly suppress the immune response and enhance epidermal differentiation to restore the barrier.

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Section: Discussionmentioning

confidence: 99%

Connexin 26 regulates epidermal barrier and wound remodeling and promotes psoriasiform response

Djalilian¹

2006

Journal of Clinical Investigation

115

107

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“…1 Maternal steroid administration has also been shown to accelerate skin maturation in rats. 16,17 The skin of all newborns is sterile at birth, 1 with colonization beginning directly after birth. Colonization counts rise rapidly during the first 7 days of life and are unrelated to skin maturity.…”

Section: Discussionmentioning

confidence: 99%

The Effect of Application of Aquaphor on Skin Condition, Fluid Requirements, and Bacterial Colonization in Very Low Birth Weight Infants

et al. 1999

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OBJECTIVE:To determine the effects of repeated application of an occlusive ointment on the skin of very low birth weight infants. STUDY DESIGN:Nineteen neonates of 26 to 30 weeks gestational age were randomly assigned to receive topical Aquaphor ointment twice daily for 2 weeks or to receive standard skin care. Skin quality, fluid requirements, and skin bacterial colonization counts were assessed. RESULTS:Infants treated with Aquaphor had significantly improved skin condition scores versus controls (p ϭ 0.002). Aquaphor improved skin scores over time (p ϭ 0.012) in treated infants, whereas skin scores of untreated infants worsened before eventually healing. There were no significant differences in total fluid requirements, urine output, serum sodium concentrations, skin bacterial counts, fungal counts, or colonization patterns between treated and control infants in either gestational age cohort. CONCLUSION:Aquaphor ointment, used during the first two postnatal weeks, improved skin condition in infants of 26 to 30 weeks' gestation without changing skin bacterial flora. We speculate that improved skin condition may limit transepidermal water loss and decrease portals of entry for pathogens, thereby potentially decreasing fluid and electrolyte imbalances and sepsis in very low birth weight infants.Neonatal intensive care unit (NICU) providers are continually challenged by the task of providing skin care to the very low birth weight (VLBW) infant. Intact skin is the premature infant's principal barrier to infection, absorption of chemicals, and fluid loss. 1 Skin permeability is inversely proportional to the degree of prematurity. 1 Increased skin permeability predisposes the VLBW infant to increased transepidermal water loss (TEWL), to absorption of commonly used topical agents such as povidone-iodine and alcohol, and to mechanical and thermal injury and infection. 2 The large ratio of surface area to body weight, in conjunction with an immature stratum corneum, compounds TEWL. 3 Increased TEWL can, in turn, result in clinically significant fluid and electrolyte imbalances in the first postnatal days.VLBW infants are prone to skin breakdown as a result of accidental epidermal stripping. Skin breakdown can augment the rate of TEWL, while providing a portal of entry for microorganisms that can lead to bacteremia. Infants born at Ͻ28 weeks' gestation, or with birth weight of Ͻ1000 gm, and aged Ͻ2 postnatal weeks old are at greatest risk for iatrogenic complications related to the integrity of their skin.Most NICU guidelines for the care of the skin of the VLBW infant are based on empirical or anecdotal data. There are several studies that measure efforts to decrease TEWL. These studies include the use of paraffin wax wraps, 3,4 plastic blankets, 3,5 humidity, 6 and artificial skin barriers. 7-9 All these methods have been shown to reduce TEWL. There have been few studies regarding the safe use of emollient therapy for this at-risk population, and most of the infants studied have been of Ͼ30 weeks' gestation. 10,11 Acc...

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“…In the fetal rat, lamellar bodies first appear in skin and lung on gestational d 18; secretion begins on d 19 and 20, respectively; and maturation of both tissue systems is complete by d 21 of gestation (normal parturition occurs on d 22) (15,16). Furthermore, glucocorticoids and thyroid hormone accelerate lung maturation (reviewed in reference 17), and, as we have shown, glucocorticoids accelerate epidermal barrier maturation in utero in the rat (18), and both glucocorticoids and thyroid hormone accelerate fetal rat barrier formation in vitro (19). Other hormones are also recognized to affect pulmonary development; for example, estrogen accelerates, while testosterone inhibits lung maturation (20)(21)(22)(23)(24)(25)(26).…”

Section: Introductionmentioning

confidence: 91%

Hormonal basis for the gender difference in epidermal barrier formation in the fetal rat. Acceleration by estrogen and delay by testosterone.

Hanley

Rassner²,

Jiang³

et al. 1996

J. Clin. Invest.

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Previous studies have shown that ontogeny of the epidermal permeability barrier and lung occur in parallel in the fetal rat, and that pharmacologic agents, such as glucocorticoids and thyroid hormone, accelerate maturation at comparable developmental time points. Gender also influences lung maturation, i.e., males exhibit delayed development. Sex steroid hormones exert opposite effects on lung maturation, with estrogens accelerating and androgens inhibiting. In this study, we demonstrate that cutaneous barrier formation, measured as transepidermal water loss, is delayed in male fetal rats. Administration of estrogen to pregnant mothers accelerates fetal barrier development both morphologically and functionally. Competent barriers also form sooner in skin explants incubated in estrogen-supplemented media in vitro. In contrast, administration of dihydrotestosterone delays barrier formation both in vivo and in vitro.

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Glucocorticoids accelerate fetal maturation of the epidermal permeability barrier in the rat.

Cited by 73 publications

References 46 publications

Connexin 26 regulates epidermal barrier and wound remodeling and promotes psoriasiform response

Connexin 26 regulates epidermal barrier and wound remodeling and promotes psoriasiform response

The Effect of Application of Aquaphor on Skin Condition, Fluid Requirements, and Bacterial Colonization in Very Low Birth Weight Infants

Hormonal basis for the gender difference in epidermal barrier formation in the fetal rat. Acceleration by estrogen and delay by testosterone.

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