{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,25]],"date-time":"2026-02-25T06:42:25Z","timestamp":1772001745750,"version":"3.50.1"},"reference-count":27,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2024,1,29]],"date-time":"2024-01-29T00:00:00Z","timestamp":1706486400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2024,1,29]],"date-time":"2024-01-29T00:00:00Z","timestamp":1706486400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81803130"],"award-info":[{"award-number":["81803130"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82003348"],"award-info":[{"award-number":["82003348"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100010098","name":"Shanghai Association for Science and Technology","doi-asserted-by":"publisher","award":["21Y11905100"],"award-info":[{"award-number":["21Y11905100"]}],"id":[{"id":"10.13039\/100010098","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Skin Research and Technology"],"published-print":{"date-parts":[[2024,2]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Prurigo nodularis (PN) is a chronic inflammatory skin disorder that is characterized by extremely itchy nodules. Proadrenomedullin N\u2010terminal 20 (PAMP) activates mast cell degranulation via Mas\u2010related G protein\u2010coupled receptor X2 (MRGPRX2), which is associated with pruritus in allergic contact dermatitis. However, the mechanisms underlying the action of PAMP and MRGPRX2 in PN remain unclear.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>To determine the role of PAMP\u2010induced mast cell activation via MRGPRX2 (mouse homologous Mrgprb2) in PN.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>The expression of PAMP and the number of MRGPRX2\u2010expressing mast cells in the skin biopsies of patients with PN, atopic dermatitis (AD), and healthy participants were analyzed using immunohistochemistry and immunofluorescence, respectively. The biphasic response of PAMP9\u201020 mediated by Mrgprb2 in mouse peritoneal mast cells (PMC) was validated in vitro using qRT\u2010PCR, ELISA, flow cytometry, and siRNA techniques.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>PAMP expression and the number of MRGPRX2+ mast cells in lesional PN skin, but not in AD, were elevated compared to healthy skin. PAMP9\u201020 mediates the immediate and delayed phase responses of PMC, such as degranulation, histamine and \u03b2\u2010hexosaminidase release, and secretion of inflammatory factors such as CCL2, TNF\u2010\u03b1, and GM\u2010CSF. These effects were inhibited when Mrgprb2 expression was silenced. Silencing Mrgprb2 did not affect the biphasic response of PMC that was induced by IgE\u2010Fc\u03b5RI activation.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>The results show that PAMP mediates mouse mast cell activation via Mrgprb2, which may be involved in the pathogenesis of PN. The PAMP\/ Mrgprb2 pathway, independent of classical IgE signaling, could be developed as a candidate drug target for treating PN.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/srt.13588","type":"journal-article","created":{"date-parts":[[2024,1,29]],"date-time":"2024-01-29T05:09:59Z","timestamp":1706504999000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["New insight into prurigo nodularis: Proadrenomedullin N\u2010terminal 20 peptide mediates mouse mast cell activation via Mrgprb2"],"prefix":"10.1111","volume":"30","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6524-5058","authenticated-orcid":false,"given":"Yixin","family":"Shao","sequence":"first","affiliation":[{"name":"Department of Dermatology Huashan Hospital Fudan University  Shanghai China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zijing","family":"Xiao","sequence":"additional","affiliation":[{"name":"Department 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