Serine protease signaling of epidermal permeability barrier homeostasis

DC FieldValueLanguage
dc.contributor.authorHachem, Jean-Pierre
dc.contributor.authorHouben, Evi
dc.contributor.authorCrumrine, Debra
dc.contributor.authorMan, Mao-Quiang
dc.contributor.authorSchurer, Nanna
dc.contributor.authorRoelandt, Truus
dc.contributor.authorChoi, Eung H.
dc.contributor.authorUchida, Yoshikazu
dc.contributor.authorBrown, Barbara E.
dc.contributor.authorFeingold, Kenneth R.
dc.contributor.authorElias, Peter M.
dc.date.accessioned2021-12-23T16:16:49Z-
dc.date.available2021-12-23T16:16:49Z-
dc.date.issued2006
dc.identifier.issn0022202X
dc.identifier.urihttps://osnascholar.ub.uni-osnabrueck.de/handle/unios/12060-
dc.description.abstractEvidence is growing that protease-activated receptor-2 (PAR-2) plays a key role in epithelial inflammation. We hypothesized here that PAR-2 plays a central role in epidermal permeability barrier homeostasis by mediating signaling from serine proteases (SP) in the stratum corneum (SC). Since the SC contains tryptic- and chymotryptic-like activity, we assessed the influence of SP activation/inhibition on barrier function. Acute barrier disruption increases SP activity and blockade by topical SP inhibitors (SPI) accelerates barrier recovery after acute abrogation. This improvement in barrier function is due to accelerated lamellar body (LB) secretion. Since tryptic SP signal certain downstream responses through PAR-2, we assessed its potential role in mediating the negative effects of SP on permeability barrier. Firstly, PAR-2 is expressed in the outer nucleated layers of the epidermis and most specifically under basal condition to the lipid raft (LR) domains. Secondly, tape stripping-induced barrier abrogation provokes PAR-2 activation, as shown by receptor internalization (i.e. receptor movement from LR to cytolpasmic domains). Thirdly, topical applications of PAR-2 agonist peptide, SLIGRL, delay permeability barrier recovery and inhibit LB secretion, while, conversely, PAR-2 knockout mice display accelerated barrier recovery kinetics and enhanced LB secretion, paralleled by increased LR formation and caveolin-1 expression. These results demonstrate first, the importance of SP/SPI balance for normal permeability barrier homeostasis, and second, they identify PAR-2 as a novel signaling mechanism of permeability barrier, that is, of response linked to LB secretion.
dc.description.sponsorshipEUNICE 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 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) [R01AR019098, R01AR049932, P01AR039448] Funding Source: NIH RePORTER; NIAMS NIH HHSUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Institute of Arthritis & Musculoskeletal & Skin Diseases (NIAMS) [AR39448, AR19098, AR049932] Funding Source: Medline; NICHD NIH HHSUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD) [HD29706] Funding Source: Medline; PHS HHSUnited States Department of Health & Human ServicesUnited States Public Health Service [AIO59311] Funding Source: Medline
dc.language.isoen
dc.publisherNATURE PUBLISHING GROUP
dc.relation.ispartofJOURNAL OF INVESTIGATIVE DERMATOLOGY
dc.subjectCALCIUM-METABOLISM
dc.subjectCERAMIDE SYNTHESIS
dc.subjectCHILDHOOD ATOPIC-DERMATITIS
dc.subjectDermatology
dc.subjectKERATINOCYTE DIFFERENTIATION
dc.subjectLAMELLAR BODIES
dc.subjectMOLECULAR-CLONING
dc.subjectMURINE EPIDERMIS
dc.subjectPROTEINASE-ACTIVATED RECEPTOR-2
dc.subjectSTRATUM-CORNEUM
dc.subjectTISSUE DISTRIBUTION
dc.titleSerine protease signaling of epidermal permeability barrier homeostasis
dc.typejournal article
dc.identifier.doi10.1038/sj.jid.5700351
dc.identifier.isiISI:000241359200020
dc.description.volume126
dc.description.issue9
dc.description.startpage2074
dc.description.endpage2086
dc.publisher.place75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA
dcterms.isPartOf.abbreviationJ. Invest. Dermatol.
dcterms.oaStatusBronze
crisitem.author.deptFB 08 - Humanwissenschaften-
crisitem.author.deptidfb08-
crisitem.author.parentorgUniversität Osnabrück-
crisitem.author.netidScNa997-
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