{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T16:16:22Z","timestamp":1791994582418,"version":"4.4.0"},"reference-count":57,"publisher":"Wiley","issue":"22","license":[{"start":{"date-parts":[[2020,9,21]],"date-time":"2020-09-21T00:00:00Z","timestamp":1600646400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["EXC 2167\u2010390884018 EXC 306 GRK 1727 EXC 2167"],"award-info":[{"award-number":["EXC 2167\u2010390884018 EXC 306 GRK 1727 EXC 2167"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002322","name":"Coordena\u00e7\u00e3o de Aperfei\u00e7oamento de Pessoal de N\u00edvel Superior","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100002322","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["bpspubs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["British J Pharmacology"],"published-print":{"date-parts":[[2020,11]]},"abstract":"<jats:sec><jats:title>Background and Purpose<\/jats:title><jats:p>Pemphigus is caused by autoantibodies against desmoglein (Dsg) 1, Dsg3, and\/or non\u2010Dsg antigens. Pemphigus vulgaris (PV) is the most common manifestation of pemphigus, with painful erosions on mucous membranes. In most cases, blistering also occurs on the skin, leading to areas of extensive denudation. Despite improvements in pemphigus treatment, time to achieve remission is long, severe adverse events are frequent and 20% of patients do not respond adequately. Current clinical developments focus exclusively on modulating B cell function or autoantibody half\u2010life. However, topical modulation of PV autoantibody\u2010induced blistering is an attractive target because it could promptly relieve symptoms.<\/jats:p><\/jats:sec><jats:sec><jats:title>Experimental Approach<\/jats:title><jats:p>To address this issue, we performed an unbiased screening in a complex biological system using 141 low MW inhibitors from a chemical library. Specifically, we evaluated PV IgG\u2010induced Dsg3 internalization in HaCaT keratinocytes. Validation of the 20 identified compounds was performed using keratinocyte fragmentation assays, as well as a human skin organ culture (HSOC) model.<\/jats:p><\/jats:sec><jats:sec><jats:title>key Results<\/jats:title><jats:p>Overall, this approach led to the identification of four molecules involved in PV IgG\u2010induced skin pathology: MEK1, TrkA, PI3K\u03b1, and VEGFR2.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion and Implications<\/jats:title><jats:p>This unbiased screening revealed novel mechanisms by which PV autoantibodies induce blistering in keratinocytes and identified new treatment targets for this severe and potentially life\u2010threatening skin disease.<\/jats:p><\/jats:sec>","DOI":"10.1111\/bph.15233","type":"journal-article","created":{"date-parts":[[2020,8,26]],"date-time":"2020-08-26T02:58:45Z","timestamp":1598410725000},"page":"5114-5130","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":29,"title":["Identification of novel therapeutic targets for blocking acantholysis in pemphigus"],"prefix":"10.1111","volume":"177","author":[{"given":"Imke A.K.","family":"Burmester","sequence":"first","affiliation":[{"name":"L\u00fcbeck Institute of Experimental Dermatology University of L\u00fcbeck  L\u00fcbeck Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah","family":"Flaswinkel","sequence":"additional","affiliation":[{"name":"L\u00fcbeck Institute of Experimental Dermatology University of L\u00fcbeck  L\u00fcbeck 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