{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,20]],"date-time":"2026-03-20T19:43:36Z","timestamp":1774035816723,"version":"3.50.1"},"reference-count":44,"publisher":"MDPI AG","issue":"19","license":[{"start":{"date-parts":[[2021,10,7]],"date-time":"2021-10-07T00:00:00Z","timestamp":1633564800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Glycoprotein non-metastatic melanoma protein B (GPNMB) is a type I transmembrane glycoprotein that plays an important role in cancer metastasis and osteoblast differentiation. In the skin epidermis, GPNMB is mainly expressed in melanocytes and plays a critical role in melanosome formation. In our previous study, GPNMB was also found to be expressed in skin epidermal keratinocytes. In addition, decreased GPNMB expression was observed in the epidermis of lesional skin of patients with vitiligo. However, the exact role of keratinocyte-derived GPNMB and its effect on vitiligo is still unknown. In this study, we demonstrated that GPNMB expression was also decreased in rhododendrol-induced leukoderma, as seen in vitiligo. The extracellular soluble form of GPNMB (sGPNMB) was found to protect melanocytes from cytotoxicity and the impairment of melanogenesis induced by oxidative stress. Furthermore, the effect of rGPNMB was not altered by the knockdown of CD44, which is a well-known receptor of GPNMB, but accompanied by the suppressed phosphorylation of AKT but not ERK, p38, or JNK. In addition, we found that oxidative stress decreased both transcriptional GPNMB expression and sGPNMB protein expression in human keratinocytes. Our results suggest that GPNMB might provide novel insights into the mechanisms related to the pathogenesis of vitiligo and leukoderma.<\/jats:p>","DOI":"10.3390\/ijms221910843","type":"journal-article","created":{"date-parts":[[2021,10,8]],"date-time":"2021-10-08T21:23:55Z","timestamp":1633728235000},"page":"10843","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["GPNMB Extracellular Fragment Protects Melanocytes from Oxidative Stress by Inhibiting AKT Phosphorylation Independent of CD44"],"prefix":"10.3390","volume":"22","author":[{"given":"Qianqian","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Pigmentation Research and Therapeutics, Graduate School of Medicine, Osaka City University, Osaka 5450051, Japan"},{"name":"Department of Dermatology, Huashan Hospital, Fudan University, Shanghai 200040, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"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 City University, Osaka 5450051, Japan"},{"name":"Biological Science Research Laboratories, Kao Corporation, Kanagawa 2500002, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"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 City University, Osaka 5450051, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sylvia","family":"Lai","sequence":"additional","affiliation":[{"name":"Department of Pigmentation Research and Therapeutics, Graduate School of Medicine, Osaka City University, Osaka 5450051, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yukiko","family":"Mizutani","sequence":"additional","affiliation":[{"name":"Department of Cosmetic Health Science, Gifu Pharmaceutical University, Gifu 5011196, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Arunasiri","family":"Iddamalgoda","sequence":"additional","affiliation":[{"name":"Department of Cosmetic Health Science, Gifu Pharmaceutical University, Gifu 5011196, Japan"},{"name":"Department of Research and Development, Ichimaru Pharcos Co. Ltd., Motosu, Gifu 5010475, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jiao","family":"Guo","sequence":"additional","affiliation":[{"name":"Department of Pigmentation Research and Therapeutics, Graduate School of Medicine, Osaka City University, Osaka 5450051, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Asako","family":"Yamamoto","sequence":"additional","affiliation":[{"name":"Department of Pigmentation Research and Therapeutics, Graduate School of Medicine, Osaka City University, Osaka 5450051, Japan"},{"name":"Department of Dermatology, Graduate School of Medicine, Osaka City University, Osaka 5458585, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daiki","family":"Murase","sequence":"additional","affiliation":[{"name":"Department of Pigmentation Research and Therapeutics, Graduate School of Medicine, Osaka City University, Osaka 5450051, Japan"},{"name":"Biological Science Research Laboratories, Kao Corporation, Kanagawa 2500002, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yoshito","family":"Takahashi","sequence":"additional","affiliation":[{"name":"Department of Pigmentation Research and Therapeutics, Graduate School of Medicine, Osaka City University, Osaka 5450051, Japan"},{"name":"Biological Science Research Laboratories, Kao Corporation, Kanagawa 2500002, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Leihong","family":"Xiang","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Huashan Hospital, Fudan University, Shanghai 200040, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4996-5693","authenticated-orcid":false,"given":"Shintaro","family":"Inoue","sequence":"additional","affiliation":[{"name":"Department of Cosmetic Health Science, Gifu Pharmaceutical University, Gifu 5011196, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daisuke","family":"Tsuruta","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Graduate School of Medicine, Osaka City University, Osaka 5458585, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ichiro","family":"Katayama","sequence":"additional","affiliation":[{"name":"Department of Pigmentation Research and Therapeutics, Graduate School of Medicine, Osaka City University, Osaka 5450051, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2021,10,7]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"15011","DOI":"10.1038\/nrdp.2015.11","article-title":"Vitiligo","volume":"1","author":"Picardo","year":"2015","journal-title":"Nat. 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