title: Acute acidification of stratum corneum membrane domains using polyhydroxyl acids improves lipid processing and inhibits degradation of corneodesmosomes.
abstract: Neutralization of the normally acidic stratum corneum (SC) has deleterious consequences for permeability barrier homeostasis and SC integrity/cohesion attributable to serine proteases (SPs) activation leading to deactivation/degradation of lipid-processing enzymes and corneodesmosomes (CD). As an elevated pH compromises SC structure and function, we asked here whether SC hyperacidification would improve the structure and function. We lowered the pH of mouse SC using two polyhydroxyl acids (PHA), lactobionic acid (LBA), or gluconolactone (GL). Applications of the PHA reduced the pH at all levels of SC of hairless mouse, with further selective acidification of SC membrane domains, as shown by fluorescence lifetime imaging. Hyperacidification improved permeability barrier homeostasis, attributable to increased activities of two key membrane-localized, ceramide-generating hydrolytic enzymes (beta-glucocerebrosidase and acidic sphingomyelinase), which correlated with accelerated extracellular maturation of SC lamellar membranes. Hyperacidification generated "supernormal" SC integrity/cohesion, attributable to an SP-dependent decreased degradation of desmoglein-1 (DSG1) and the induction of DSG3 expression in lower SC. As SC hyperacidification improves the structure and function, even of normal epidermis, these studies lay the groundwork for an assessment of the potential utility of SC acidification as a therapeutic strategy for inflammatory dermatoses, characterized by abnormalities in barrier function, cohesion, and surface pH.
authors.affiliation: Department of Dermatology, Universitair Ziekenhuis Brussel-Vrije Universiteit Brussel, Brussels, Belgium. jeanpierre.hachem@uzbrussel.be
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Hachem
authors.forename: Truus
authors.initials: T
authors.lastname: Roelandt
authors.forename: Nanna
authors.initials: N
authors.lastname: Schürer
authors.forename: Xu
authors.initials: X
authors.lastname: Pu
authors.forename: Joachim
authors.initials: J
authors.lastname: Fluhr
authors.forename: Christina
authors.initials: C
authors.lastname: Giddelo
authors.forename: Mao-Qiang
authors.initials: MQ
authors.lastname: Man
authors.forename: Debra
authors.initials: D
authors.lastname: Crumrine
authors.forename: Diane
authors.initials: D
authors.lastname: Roseeuw
authors.forename: Kenneth R
authors.initials: KR
authors.lastname: Feingold
authors.forename: Theodora
authors.initials: T
authors.lastname: Mauro
authors.forename: Peter M
authors.initials: PM
authors.lastname: Elias
mesh_terms: D000818:Animals; D001706:Biopsy; D002462:Cell Membrane / Q000378:metabolism; D003896:Desmosomes / Q000378:metabolism*; D004187:Disaccharides / Q000494:pharmacology*; D004817:Epidermis / Q000187:drug effects* / Q000378:metabolism*; D005942:Gluconates / Q000494:pharmacology*; D006863:Hydrogen-Ion Concentration; D007783:Lactones; D008055:Lipids / Q000737:chemistry*; D008297:Male; D021962:Membrane Microdomains / Q000378:metabolism; D051379:Mice; D008812:Mice, Hairless; D008856:Microscopy, Fluorescence / Q000379:methods; D012867:Skin / Q000378:metabolism
chemical_list: D004187:Disaccharides; D005942:Gluconates; D007783:Lactones; D008055:Lipids; C005608:lactobionic acid; C010730:beta-glucono-1,5-lactone