{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,12]],"date-time":"2026-05-12T21:59:08Z","timestamp":1778623148403,"version":"3.51.4"},"reference-count":61,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2024,5,29]],"date-time":"2024-05-29T00:00:00Z","timestamp":1716940800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["CIMB"],"abstract":"<jats:p>Melanocytes, located in the epidermis\u2019 basal layer, are responsible for melanin pigment production, crucial for skin coloration and protection against UV radiation-induced damage. Melanin synthesis is intricately regulated by various factors, including the Wnt signaling pathway, particularly mediated by the microphthalmia-associated transcription factor (MITF). While MITF is recognized as a key regulator of pigmentation, its regulation by the Wnt pathway remains poorly understood. This study investigates the role of Sfrp5pepD, a peptide antagonist of the Wnt signaling pathway, in modulating melanogenesis and its potential therapeutic implications for pigmentary disorders. To tackle this issue, we investigated smaller peptides frequently utilized in cosmetics or pharmaceuticals. Nevertheless, there is a significant scarcity of reports on peptides associated with melanin-related signal modulation or inhibiting melanin production. Results indicate that Sfrp5pepD effectively inhibits Wnt signaling by disrupting the interaction between Axin-1 and \u03b2-catenin, thus impeding downstream melanogenic processes. Additionally, Sfrp5pepD suppresses the interaction between MITF and \u03b2-catenin, inhibiting their nuclear translocation and downregulating melanogenic enzyme expression, ultimately reducing melanin production. These inhibitory effects are validated in cell culture models suggesting potential clinical applications for hyperpigmentation disorders. Overall, this study elucidates the intricate interplay between Wnt signaling and melanogenesis, highlighting Sfrp5pepD as a promising therapeutic agent for pigmentary disorders. Sfrp5pepD, with a molecular weight of less than 500 Da, is anticipated to penetrate the skin unlike SFRPs. This suggests a strong potential for their use as cosmetics or transdermal absorption agents. Additional investigation into its mechanisms and clinical significance is necessary to enhance its effectiveness in addressing melanin-related skin conditions.<\/jats:p>","DOI":"10.3390\/cimb46060324","type":"journal-article","created":{"date-parts":[[2024,6,3]],"date-time":"2024-06-03T12:29:47Z","timestamp":1717417787000},"page":"5420-5435","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Small Peptide Derived from SFRP5 Suppresses Melanogenesis by Inhibiting Wnt Activity"],"prefix":"10.3390","volume":"46","author":[{"given":"Yoon-Seo","family":"Choi","sequence":"first","affiliation":[{"name":"Graduate School-Interdisciplinary Program in Biocosmetics, Sungkyunkwan University, Suwon 16419, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jin-Gwen","family":"Hong","sequence":"additional","affiliation":[{"name":"Research and Development Department, Benex Co., Ltd., Cheongju 28118, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dong-Young","family":"Lim","sequence":"additional","affiliation":[{"name":"R&D Center, Supadelixir Co., Ltd., Chuncheon 24232, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Min-Seo","family":"Kim","sequence":"additional","affiliation":[{"name":"R&D Center, Supadelixir Co., Ltd., Chuncheon 24232, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sang-Hoon","family":"Park","sequence":"additional","affiliation":[{"name":"Department of Plastic Surgery, ID Hospital, Gangnam 06039, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hee-Cheol","family":"Kang","sequence":"additional","affiliation":[{"name":"Materials Division Affiliated Research Center, GFC Life Science Co., Ltd., Hwaseong 18471, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0439-8189","authenticated-orcid":false,"given":"Won-Sang","family":"Seo","sequence":"additional","affiliation":[{"name":"Materials Division Affiliated Research Center, GFC Life Science Co., Ltd., Hwaseong 18471, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5073-2619","authenticated-orcid":false,"given":"Jongsung","family":"Lee","sequence":"additional","affiliation":[{"name":"Molecular Dermatology Laboratory, Department of Integrative Biotechnology, College of Biotechnology and Bioengineering, Sungkyunkwan University, Suwon 16419, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2024,5,29]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"316","DOI":"10.1111\/pcmr.12080","article-title":"Cellular and molecular mechanisms controlling the migration of melanocytes and melanoma cells","volume":"26","author":"Bonaventure","year":"2013","journal-title":"Pigment. 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