{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T18:14:24Z","timestamp":1789496064593,"version":"build-2803163510"},"reference-count":16,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2021,6,14]],"date-time":"2021-06-14T00:00:00Z","timestamp":1623628800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100004312","name":"Eli Lilly and Company","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100004312","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100006484","name":"AbbVie Deutschland","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100006484","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Journal of Dermatology"],"published-print":{"date-parts":[[2021,9]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Psoriasis, an immune\u2010mediated inflammatory disease, is characterized by keratinocyte hyperproliferation. Tumor necrosis factor (TNF)\u2010\u03b1, interleukin (IL)\u201023, and IL\u201017A play critical roles in the pathogenesis of psoriasis. IL\u201017A secreted by T\u2010helper 17 acts more directly against keratinocytes than TNF\u2010\u03b1 or IL\u201023 do. Regarding the receptors of cytokines, fibroblasts also express receptors against IL\u201017A and TNF\u2010\u03b1, and induce the production of growth factors. Epiregulin (EREG), an epidermal growth factor receptor ligand, is produced by both keratinocytes and fibroblasts. EREG enhances keratinocyte proliferation and differentiation. We hypothesized that fibroblasts stimulated with IL\u201017A and\/or TNF\u2010\u03b1 may play a role in epidermal hyperproliferation through the production of epidermal growth factors in psoriasis. The mRNA expression of EREG was found to be significantly upregulated by co\u2010stimulation with IL\u201017A and TNF\u2010\u03b1 (mean, 49.2\u2010fold). Furthermore, the stimulation with TNF\u2010\u03b1 alone, but not IL\u201017A alone, induced significant increases. Immunofluorescent staining demonstrated that the protein expression level of EREG was also increased in fibroblasts stimulated with these cytokines. Stimulation with EREG significantly enhanced keratinocyte proliferation <jats:italic>in vitro<\/jats:italic>. In human psoriatic patients\u2019 skin, immunofluorescence staining of EREG showed significantly high intensity in the dermis of lesional skin. In conclusion, cytokine stimulation with TNF\u2010\u03b1 and IL\u201017A induces the overexpression of EREG from dermal fibroblasts in the lesional skin of psoriasis, and plays a role in epidermal hyperproliferation.<\/jats:p>","DOI":"10.1111\/1346-8138.16003","type":"journal-article","created":{"date-parts":[[2021,6,15]],"date-time":"2021-06-15T05:24:31Z","timestamp":1623734671000},"page":"1433-1438","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":20,"title":["Possible role of epiregulin from dermal fibroblasts in the keratinocyte hyperproliferation of psoriasis"],"prefix":"10.1111","volume":"48","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8781-2735","authenticated-orcid":false,"given":"Hiroaki","family":"Iwata","sequence":"first","affiliation":[{"name":"Department of Dermatology Faculty of Medicine and Graduate School of Medicine Hokkaido University Sapporo 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Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2021,6,14]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20150204"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jdermsci.2006.08.010"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm1162"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrd3794"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12016-018-8702-3"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1042\/bj3260069"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.270.13.7495"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jdermsci.2020.01.003"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.jid.5700786"},{"key":"e_1_2_7_11_1","first-page":"11","article-title":"Interplay between keratinocytes and fibroblasts: a systematic review providing a new angle for understanding skin fibrotic disorders","author":"Russo B","year":"2020","journal-title":"Front Immunol"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0066725"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0014-2999(97)81928-0"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13046-019-1277-x"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1152\/physiolgenomics.00045.2008"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI63748"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.semcdb.2014.03.005"}],"container-title":["The Journal of 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