{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T12:32:39Z","timestamp":1791549159266,"version":"4.3.4"},"reference-count":42,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2022,11,9]],"date-time":"2022-11-09T00:00:00Z","timestamp":1667952000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81773305"],"award-info":[{"award-number":["81773305"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Experimental Dermatology"],"published-print":{"date-parts":[[2023,2]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Melanocytes stimulated by ultraviolet radiation (UVR) produce melanin and melanosomes, which causes skin pigmentation and acts as an important physiological defence process for photoprotection. Neutral luminal pH of melanosomes is critical for providing optimal conditions for the rate\u2010limiting, pH\u2010sensitive melanin synthesizing enzyme tyrosinase (TYR). As a major component of extraocular phototransduction pathway, transient receptor potential ankyrin1 (TRPA1) can be activated by ultraviolet B (UVB) and reported to be expressed in melanocytes. However, whether TRPA1 is involved in the regulation of melanogenesis remains unclear. Melanogenic activity of TRPA1 was evaluated in primary normal human epidermal melanocytes (HEMs) and murine B16\u2010F10 cell cultures, and the effects of topical applications of TRPA1 specific agonist and antagonist on UVB\u2010induced skin pigmentation were confirmed on in vivo guinea pig models. Calcium (Ca<jats:sup>2+<\/jats:sup>) imaging and pH imaging were performed to analyse the effects of TRPA1 on intracellular Ca<jats:sup>2+<\/jats:sup> concentration ([Ca<jats:sup>2+<\/jats:sup>]<jats:sub>ic<\/jats:sub>) and melanosome luminal pH. TRPA1 regulated melanin synthesis, UVB\u2010induced Ca<jats:sup>2+<\/jats:sup> influx and melanosome luminal pH in HEMs and B16\u2010F10 cells. Topical treatment of TRPA1 specific agonist JT010 increased UVB\u2010induced skin pigmentation in guinea pigs, while topical using of TRPA1 selective antagonist HC\u2010030031 mitigated such pigmentation. Our results indicated that TRPA1 activated by UVB enhanced the skin pigmentation, most likely by regulating the [Ca<jats:sup>2+<\/jats:sup>]<jats:sub>ic<\/jats:sub> and the melanosomal pH, consequently influencing the enzymatic activity of TYR. Therefore, the results suggest TRPA1 as a potential therapeutic target in the treatment of skin pigmented disorders that are at high risk under UVB irradiation.<\/jats:p>","DOI":"10.1111\/exd.14693","type":"journal-article","created":{"date-parts":[[2022,10,27]],"date-time":"2022-10-27T18:39:08Z","timestamp":1666895948000},"page":"165-176","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["<scp>TRPA1<\/scp> promotes <scp>UVB\u2010induced<\/scp> skin pigmentation by regulating melanosome luminal <scp>pH<\/scp>"],"prefix":"10.1111","volume":"32","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9308-7181","authenticated-orcid":false,"given":"Wei","family":"Wu","sequence":"first","affiliation":[{"name":"Department of Dermatology First Affiliated Hospital of Dalian Medical University  Dalian 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