{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,17]],"date-time":"2026-06-17T21:17:22Z","timestamp":1781731042923,"version":"3.54.5"},"reference-count":45,"publisher":"MDPI AG","issue":"15","license":[{"start":{"date-parts":[[2019,7,26]],"date-time":"2019-07-26T00:00:00Z","timestamp":1564099200000},"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>To characterize the pathobiology of solar lentigos (SLs), analyses by semiquantitative RT-PCR, Western blotting, and immunohistochemistry revealed the upregulated expression of endothelin (EDN)-1\/endothelin B receptors (EDNBRs), stem cell factor (SCF)\/c-KIT, and tumor necrosis factor (TNF)\u03b1 in the lesional epidermis, which contrasted with the downregulated expression of interleukin (IL) 1\u03b1. These findings strongly support the hypothesis that previous repeated UVB exposure triggers keratinocytes to continuously produce TNF\u03b1. TNF\u03b1 then stimulates the secretion of EDNs and the production of SCF in an autocrine fashion, leading to the continuous melanogenic activation of neighboring melanocytes, which causes SLs. A clinical study of 36 patients with SLs for six months treated with an M. Chamomilla extract with a potent ability to abrogate the EDN1-induced increase in DNA synthesis and melanization of human melanocytes in culture revealed a significant improvement in pigment scores and color differences expressed as L values. Another clinical study using a tyrosinase inhibitor L-ascorbate-2-phosphate 3 Na (ASP) demonstrated that L values of test lotion (6% APS)-treated skin significantly increased in SLs and in non-lesional skin with a significantly higher \u0394L value in SLs when compared with non-lesional skin. The sum of these findings strongly suggests that combined topical treatment with EDN signaling blockers and tyrosinase inhibitors is a desirable therapeutic choice for SLs.<\/jats:p>","DOI":"10.3390\/ijms20153666","type":"journal-article","created":{"date-parts":[[2019,7,26]],"date-time":"2019-07-26T08:45:39Z","timestamp":1564130739000},"page":"3666","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":37,"title":["Melanocyte Activation Mechanisms and Rational Therapeutic Treatments of Solar Lentigos"],"prefix":"10.3390","volume":"20","author":[{"given":"Genji","family":"Imokawa","sequence":"first","affiliation":[{"name":"Center for Bioscience Research &amp; Education, Utsunomiya University, 350 Mine Utsunomiya, Tochigi 321-8505, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2019,7,26]]},"reference":[{"key":"ref_1","first-page":"43","article-title":"Hyperpigmentation mechanisms involved in UVB-melanosis and solar lentigo and clinical effects of Chamomilla extract on the pigmentation","volume":"98","author":"Kawashima","year":"2005","journal-title":"Mon. 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