Acute Acidification of Stratum Corneum Membrane Domains Using Polyhydroxyl Acids Improves Lipid Processing and Inhibits Degradation of Corneodesmosomes

DC FieldValueLanguage
dc.contributor.authorHachem, Jean-Pierre
dc.contributor.authorRoelandt, Truus
dc.contributor.authorSchuerer, Nanna
dc.contributor.authorPu, Xu
dc.contributor.authorFluhr, Joachim
dc.contributor.authorGiddelo, Christina
dc.contributor.authorMan, Mao-Qiang
dc.contributor.authorCrumrine, Debra
dc.contributor.authorRoseeuw, Diane
dc.contributor.authorFeingold, Kenneth R.
dc.contributor.authorMauro, Theodora
dc.contributor.authorElias, Peter M.
dc.date.accessioned2021-12-23T16:21:58Z-
dc.date.available2021-12-23T16:21:58Z-
dc.date.issued2010
dc.identifier.issn0022202X
dc.identifier.urihttps://osnascholar.ub.uni-osnabrueck.de/handle/unios/14103-
dc.description.abstractNeutralization 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.
dc.description.sponsorshipNIHUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USA [AR19098, HD29706, AI059311, AR049932, AR39448]; Medical Research Service, Department of Veterans AffairsUS Department of Veterans Affairs; Vrije Universiteit Brussel [1006]; Flemish Funds for Scientific ResearchFWO [FWO306]; Fundamenteel Klinisch Mandaat; EUNICE KENNEDY SHRIVER NATIONAL INSTITUTE OF CHILD HEALTH &HUMAN DEVELOPMENTUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD) [R01HD029706] Funding Source: NIH RePORTER; NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASESUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Institute of Allergy & Infectious Diseases (NIAID) [R01AI059311] Funding Source: NIH RePORTER; NATIONAL INSTITUTE OF ARTHRITIS AND MUSCULOSKELETAL AND SKIN DISEASESUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Institute of Arthritis & Musculoskeletal & Skin Diseases (NIAMS) [R01AR049932, P01AR039448, R01AR019098] Funding Source: NIH RePORTER; Ms Jerelyn Magnusson and Ms Joan Wakefield provided excellent editorial assistance. These studies were supported by NIH Grants AR19098, HD29706, AI059311, AR049932, and AR39448 (PP); the Medical Research Service, Department of Veterans Affairs; the Vrije Universiteit Brussel (OZR Grant 1006, Gepts Funds); and the Flemish Funds for Scientific Research (FWO306). Jean-Pierre Hachem is a recipient of the FWO fellowship Fundamenteel Klinisch Mandaat.
dc.language.isoen
dc.publisherNATURE PUBLISHING GROUP
dc.relation.ispartofJOURNAL OF INVESTIGATIVE DERMATOLOGY
dc.subjectALPHA-HYDROXY-ACIDS
dc.subjectBETA-GLUCOCEREBROSIDASE ACTIVITY
dc.subjectCATHEPSIN-D
dc.subjectDermatology
dc.subjectGLYCOLIC ACID
dc.subjectHAIRLESS MICE
dc.subjectPERMEABILITY BARRIER HOMEOSTASIS
dc.subjectPH GRADIENT
dc.subjectPROTEOLYTIC CASCADE
dc.subjectSERINE PROTEASES
dc.subjectSKIN BARRIER
dc.titleAcute Acidification of Stratum Corneum Membrane Domains Using Polyhydroxyl Acids Improves Lipid Processing and Inhibits Degradation of Corneodesmosomes
dc.typejournal article
dc.identifier.doi10.1038/jid.2009.249
dc.identifier.isiISI:000273841300026
dc.description.volume130
dc.description.issue2
dc.description.startpage500
dc.description.endpage510
dc.contributor.orcid0000-0003-3610-0698
dc.contributor.orcid0000-0002-0957-4903
dc.contributor.researcheridV-5266-2019
dc.publisher.place75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
dcterms.isPartOf.abbreviationJ. Invest. Dermatol.
dcterms.oaStatusBronze, Green Accepted
crisitem.author.deptFB 08 - Humanwissenschaften-
crisitem.author.deptidfb08-
crisitem.author.parentorgUniversität Osnabrück-
crisitem.author.netidScNa997-
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