{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,6]],"date-time":"2026-05-06T11:29:12Z","timestamp":1778066952873,"version":"3.51.4"},"reference-count":76,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2023,12,7]],"date-time":"2023-12-07T00:00:00Z","timestamp":1701907200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100006483","name":"AbbVie","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100006483","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100004336","name":"Novartis","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100004336","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Experimental Dermatology"],"published-print":{"date-parts":[[2024,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Notch signalling has generated considerable interest as a pathogenetic factor and a drug target in a range of human diseases. The gamma\u2010secretase complex is crucial in the activation of Notch receptors by cleaving the intracellular domain allowing nuclear translocation. In recent years several mutations in gamma\u2010secretase components have been discovered in patients with familial hidradenitis suppurativa (HS). This has led to hypotheses that impaired Notch signalling could be an important driver for HS in general, not only in the monogenic variants. However, no study has examined in\u00a0situ Notch activation per se in HS, and some reports with conflicting results have instead been based on expression of Notch receptors or indirect measures of Notch target gene expression. In this study we established immunostaining protocols to identify native, activated Notch receptors in human skin tissue. The ability to detect changes in Notch activation was confirmed with an ex\u00a0vivo skin organ model in which signal was reduced or obliterated in tissue exposed to a gamma\u2010secretase inhibitor. Using these methods on skin biopsies from healthy volunteers and a general HS cohort we demonstrated for the first time the distribution of active Notch signalling in human apocrine\u2010bearing skin. Quantification of activated NOTCH1 &amp; NOTCH2 revealed similar levels in non\u2010lesional and peri\u2010lesional HS to that of healthy controls, thus ruling out a general defect in Notch activation in HS patients. We did find a variable but significant reduction of activated Notch in epidermis of lesional HS with a distribution that appeared related to the extent of surrounding tissue inflammation.<\/jats:p>","DOI":"10.1111\/exd.14977","type":"journal-article","created":{"date-parts":[[2023,12,8]],"date-time":"2023-12-08T00:09:58Z","timestamp":1701994198000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Detection of native, activated Notch receptors in normal human apocrine\u2010bearing skin and in hidradenitis suppurativa"],"prefix":"10.1111","volume":"33","author":[{"ORCID":"https:\/\/orcid.org\/0009-0003-8336-7712","authenticated-orcid":false,"given":"Siri Hansen","family":"Stabell","sequence":"first","affiliation":[{"name":"Institute of Clinical Medicine University of Oslo  Oslo Norway"},{"name":"Department of Dermatology Oslo University Hospital  Oslo Norway"},{"name":"Department of Pathology Oslo University Hospital  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