{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T00:19:18Z","timestamp":1790295558325,"version":"4.1.0"},"reference-count":38,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2024,5,5]],"date-time":"2024-05-05T00:00:00Z","timestamp":1714867200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Pigment Cell Melanoma Res"],"published-print":{"date-parts":[[2024,7]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Epidermal melanin unit integrity is crucial for skin homeostasis and pigmentation. Epidermal growth factor (EGF) receptor (EGFR) is a pivotal player in cell growth, wound healing, and maintaining skin homeostasis. However, its influence on skin pigmentation is relatively unexplored. This study investigates the impact and underlying mechanisms of EGFR inhibitors on skin pigmentation. We evaluated EGF and EGFR expression in various skin cells using quantitative real\u2010time PCR, Western blot, and immunofluorescence. EGF and EGFR were predominantly expressed in epidermal keratinocytes, and treatment with the EGFR tyrosine kinase inhibitors (EGFR\u2010TKIs) gefitinib and PD153035 significantly increased stem cell factor (SCF) and endothelin\u20101 (ET\u20101) expression in cultured keratinocytes. Enhanced melanocyte migration and proliferation were observed in co\u2010culture, as evidenced by time\u2010lapse live imaging and single\u2010cell tracking assays. Furthermore, topical application of gefitinib to guinea pig dorsal skin induced increased pigmentation and demonstrated efficacy in mitigating rhododendrol\u2010induced leukoderma. Suppression of EGF signaling indirectly enhanced skin pigmentation by upregulating SCF and ET\u20101 in epidermal keratinocytes. This novel mechanism highlights the pivotal role of EGF signaling in regulating skin pigmentation, and topical EGFR\u2010TKI therapy at an appropriate dose may be a promising approach for depigmentation disorder management.<\/jats:p>","DOI":"10.1111\/pcmr.13171","type":"journal-article","created":{"date-parts":[[2024,5,6]],"date-time":"2024-05-06T01:00:15Z","timestamp":1714957215000},"page":"514-529","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Effects of <scp>EGFR\u2010TKI<\/scp> on epidermal melanin unit integrity: Therapeutic implications for hypopigmented skin disorders"],"prefix":"10.1111","volume":"37","author":[{"given":"Ping","family":"Xu","sequence":"first","affiliation":[{"name":"Department of Pigmentation Research and Therapeutics, Graduate School of Medicine Osaka Metropolitan University  Osaka Japan"},{"name":"Department of Dermatology Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1578-6221","authenticated-orcid":false,"given":"Lingli","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Pigmentation Research and Therapeutics, Graduate School of Medicine Osaka Metropolitan University  Osaka Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sylvia","family":"Lai","sequence":"additional","affiliation":[{"name":"Department of Pigmentation Research and Therapeutics, Graduate School of Medicine Osaka Metropolitan University  Osaka Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fei","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Pigmentation Research and Therapeutics, Graduate School of Medicine Osaka Metropolitan University  Osaka Japan"},{"name":"Biological Science Research Laboratories Kao Corporation  Odawara Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0796-4331","authenticated-orcid":false,"given":"Yasutaka","family":"Kuroda","sequence":"additional","affiliation":[{"name":"Department of Pigmentation Research and Therapeutics, Graduate School of Medicine Osaka Metropolitan University  Osaka Japan"},{"name":"Biological Science Research Laboratories Kao Corporation  Odawara Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huimin","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Dermatology Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daisuke","family":"Tsuruta","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Graduate School of Medicine Osaka Metropolitan University  Osaka Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ichiro","family":"Katayama","sequence":"additional","affiliation":[{"name":"Department of Pigmentation Research and Therapeutics, Graduate School of Medicine Osaka Metropolitan University  Osaka Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,5,5]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpgi.00253.2004"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.0022\u2010202X.2004.23447.x"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/jid.2012.272"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM198907133210203"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(19)38983-5"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.jid.5701247"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2004.02.168"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.5070\/D327553616"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.5114\/pdia.2013.33376"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(19)83739-0"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1159\/000503758"},{"key":"e_1_2_9_13_1","first-page":"481","article-title":"The epidermal melanin unit system","volume":"147","author":"Fitzpatrick T. 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