title: Functional consequences of a neutral pH in neonatal rat stratum corneum.
abstract: At birth, neonatal stratum corneum (SC) pH is close to neutral but acidifies with maturation, which can be ascribed, in part, to secretory phospholipase A(2) and sodium/hydrogen antiporter 1 (NHE1) activities. Here we assessed the functional consequences of a neutral SC pH in a newborn rat model. While basal transepidermal water loss rates are near normal, barrier recovery (BR) rates after acute barrier disruption were delayed in newborn animals. The abnormality in barrier homeostasis could be improved by topical applications of an acidic buffer, indicating that barrier abnormality is primarily due to high SC pH. The delay in BR correlated with incompletely processed lamellar membranes and decreased activity of beta-glucocerebrosidase. Inhibition of NHE1 delayed BR after acute barrier perturbation. SC integrity was abnormal in newborn animals. Electron microscopy demonstrated decreased corneodesmosomes (CD) in newborn animals with decreased expression of desmoglein 1 and corneodesmosin. Serine protease activation appears to be responsible for CD degradation in newborn animals, because serine protease activity is increased in the SC and it can be reduced by acidification of the SC. The delay in acidification of neonatal SC results in abnormalities in permeability barrier homeostasis and SC integrity and are likely due to pH-induced modulations in enzyme activity.
authors.affiliation: Dermatology and Medical Service, Veterans Affairs Medical Center, San Francisco, California 94121, USA. fluhr@derma.uni-jena.de
authors.forename: Joachim W
authors.initials: JW
authors.lastname: Fluhr
authors.forename: Man
authors.initials: M
authors.lastname: Mao-Qiang
authors.forename: Barbara E
authors.initials: BE
authors.lastname: Brown
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Hachem
authors.forename: David G
authors.initials: DG
authors.lastname: Moskowitz
authors.forename: Marianne
authors.initials: M
authors.lastname: Demerjian
authors.forename: Marek
authors.initials: M
authors.lastname: Haftek
authors.forename: Guy
authors.initials: G
authors.lastname: Serre
authors.forename: Debra
authors.initials: D
authors.lastname: Crumrine
authors.forename: Theodora M
authors.initials: TM
authors.lastname: Mauro
authors.forename: Peter M
authors.initials: PM
authors.lastname: Elias
authors.forename: Kenneth R
authors.initials: KR
authors.lastname: Feingold
mesh_terms: D000143:Acids / Q000378:metabolism; D000818:Animals; D000831:Animals, Newborn; D015820:Cadherins / Q000378:metabolism; D051183:Desmoglein 1; D003896:Desmosomes / Q000378:metabolism / Q000648:ultrastructure; D004817:Epidermis / Q000254:growth & development* / Q000378:metabolism*; D005260:Female; D006023:Glycoproteins / Q000378:metabolism; D006706:Homeostasis / Q000502:physiology; D006863:Hydrogen-Ion Concentration; D036341:Intercellular Signaling Peptides and Proteins; D008854:Microscopy, Electron; D011247:Pregnancy; D051381:Rats; D017207:Rats, Sprague-Dawley; D012697:Serine Endopeptidases / Q000378:metabolism
chemical_list: D000143:Acids; C109656:CDSN protein, human; D015820:Cadherins; D051183:Desmoglein 1; D006023:Glycoproteins; D036341:Intercellular Signaling Peptides and Proteins; D012697:Serine Endopeptidases