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The PLAUR signaling promotes chronic pruritus.

dc.contributor.authorChen, Weiwei
dc.contributor.authorLi, Yanqing
dc.contributor.authorSteinhoff, Martin
dc.contributor.authorZhang, Wenhao
dc.contributor.authorBuddenkotte, Joerg
dc.contributor.authorBuhl, Timo
dc.contributor.authorZhu, Renkai
dc.contributor.authorYan, Xinrong
dc.contributor.authorLu, Zhiping
dc.contributor.authorXiao, Song
dc.contributor.authorWang, Jiafu
dc.contributor.authorMeng, Jianghui
dc.date.accessioned2024-07-10T15:48:43Z
dc.date.available2024-07-10T15:48:43Z
dc.identifier.pmid35596683
dc.identifier.doi10.1096/fj.202200079R
dc.identifier.urihttp://hdl.handle.net/10147/642070
dc.descriptionChronic itch is a complex sensation of the skin frequently associated with skin diseases, such as atopic dermatitis (AD) and psoriasis. Although Serpin E1 is implicated in chronic itch, its receptor and signaling pathways involved in itch are not known. In this study, the clinical relevance of a putative Serpin E1 receptor PLAUR to chronic itch, and the neuro-cutaneous Serpin E1-PLAUR signaling are explored. We found that PLAUR is overexpressed in skin specimens of human lesional AD and lesional psoriasis, and sensory neurons innervating MC903-induced AD-like murine skin. Murine PLAUR+ sensory neurons responded to Serpin E1, resulting in enrichment of numerous itch- and inflammation-related genes and their protein release. PLAUR resides in TLR2+ neurons and Serpin E1 stimulus led to transcriptional upregulation of TLR2 and its co-signaling proteins. Agonists of TLR2 propagated itch-related gene transcription including BNP, OSM, and PAR2. OSM induced acute itch in mice and promoted G-CSF and IL-8 release from human keratinocytes. Serpin E1 inhibitor reduced MC903-induced itch, epidermal hyperplasia, immunocyte infiltration, and resulted in lower transcription/expression levels of Serpin E1 and OSM. Taken together, the PLAUR-TLR2-OSM signaling promotes skin-nerve communication, cutaneous inflammation, and itch, all feeding into an aggravation of AD and exaggerated itch circuits.en_US
dc.language.isoenen_US
dc.rights© 2022 The Authors. The FASEB Journal published by Wiley Periodicals LLC on behalf of Federation of American Societies for Experimental Biology.
dc.rightsAttribution-NonCommercial-NoDerivatives 4.0 International*
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/4.0/*
dc.subjectOSMen_US
dc.subjectOSMRen_US
dc.subjectPLAURen_US
dc.subjectSerpin E1en_US
dc.subjectatopic dermatitisen_US
dc.subjecttoll-like receptoren_US
dc.titleThe PLAUR signaling promotes chronic pruritus.en_US
dc.typeArticleen_US
dc.typeOtheren_US
dc.identifier.eissn1530-6860
dc.identifier.journalFASEB journal : official publication of the Federation of American Societies for Experimental Biologyen_US
dc.source.journaltitleFASEB journal : official publication of the Federation of American Societies for Experimental Biology
dc.source.volume36
dc.source.issue6
dc.source.beginpagee22368
dc.source.endpage
refterms.dateFOA2024-07-10T15:48:45Z
dc.source.countryUnited States


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© 2022 The Authors. The FASEB Journal published by Wiley Periodicals LLC on behalf of Federation of American Societies for Experimental Biology.
Except where otherwise noted, this item's license is described as © 2022 The Authors. The FASEB Journal published by Wiley Periodicals LLC on behalf of Federation of American Societies for Experimental Biology.