{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,3]],"date-time":"2025-11-03T04:53:13Z","timestamp":1762145593207,"version":"build-2065373602"},"reference-count":43,"publisher":"MDPI AG","issue":"24","license":[{"start":{"date-parts":[[2020,12,17]],"date-time":"2020-12-17T00:00:00Z","timestamp":1608163200000},"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>Paired box gene 3 (Pax3) and cAMP responsive element-binding protein (CREB) directly interact with the cis-acting elements on the promoter of microphthalmia-associated transcription factor isoform M (MITF-M) for transcriptional activation in the melanogenic process. Tyrosinase (Tyro) is a target gene of MITF-M, and functions as a key enzyme in melanin biosynthesis. Tetrahydroquinoline carboxamide (THQC) was previously screened as an antimelanogenic candidate. In the current study, we evaluated the antimelanogenic activity of THQC in vivo and elucidated a possible mechanism. Topical treatment with THQC mitigated ultraviolet B (UVB)-induced skin pigmentation in guinea pig with decreased messenger RNA (mRNA) and protein levels of melanogenic genes such as MITF-M and Tyro. Moreover, THQC inhibited cAMP-induced melanin production in \u03b1-melanocyte-stimulating hormone (\u03b1-MSH)- or histamine-activated B16-F0 cells, in which it suppressed the expression of the MITF-M gene at the promoter level. As a mechanism, THQC normalized the protein levels of Pax3, a transcriptional activator of the MITF-M gene, in UVB-exposed and pigmented skin, as well as in \u03b1-MSH-activated B16-F0 culture. However, THQC did not affect UVB- or \u03b1-MSH-induced phosphorylation (activation) of CREB. The results suggest that suppression of the Pax3\u2013MITF-M axis might be a potential strategy in the treatment of skin pigmentary disorders that are at high risk under UVB radiation.<\/jats:p>","DOI":"10.3390\/ijms21249631","type":"journal-article","created":{"date-parts":[[2020,12,17]],"date-time":"2020-12-17T10:42:47Z","timestamp":1608201767000},"page":"9631","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Suppression of Pax3\u2013MITF-M Axis Protects from UVB-Induced Skin Pigmentation by Tetrahydroquinoline Carboxamide"],"prefix":"10.3390","volume":"21","author":[{"given":"Yong-Pyo","family":"Choi","sequence":"first","affiliation":[{"name":"College of Pharmacy, Chungbuk National University, Cheongju 28160, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ga Hyun","family":"Kim","sequence":"additional","affiliation":[{"name":"College of Pharmacy, Chungbuk National University, Cheongju 28160, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Song-Hee","family":"Kim","sequence":"additional","affiliation":[{"name":"College of Pharmacy, Chungbuk National University, Cheongju 28160, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jongseo","family":"Maeng","sequence":"additional","affiliation":[{"name":"College of Pharmacy, Chungbuk National University, Cheongju 28160, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Heesoon","family":"Lee","sequence":"additional","affiliation":[{"name":"College of Pharmacy, Chungbuk National University, Cheongju 28160, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6656-6523","authenticated-orcid":false,"given":"Sang-Bae","family":"Han","sequence":"additional","affiliation":[{"name":"College of Pharmacy, Chungbuk National University, Cheongju 28160, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ki Ho","family":"Kim","sequence":"additional","affiliation":[{"name":"Kihobio Company, Cheongju 28160, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Youngsoo","family":"Kim","sequence":"additional","affiliation":[{"name":"College of Pharmacy, Chungbuk National University, Cheongju 28160, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2020,12,17]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"193","DOI":"10.1002\/biof.29","article-title":"Physiological factors that regulate skin pigmentation","volume":"35","author":"Yamaguchi","year":"2009","journal-title":"Biofactors"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1111\/j.1600-0749.2006.00358.x","article-title":"Regulation of human skin pigmentation and responses to ultraviolet radiation","volume":"20","author":"Miyamura","year":"2007","journal-title":"Pigment Cell Res."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1992","DOI":"10.1210\/en.2017-03230","article-title":"How UV light touches the brain and endocrine system through skin, and why","volume":"159","author":"Slominski","year":"2018","journal-title":"Endocrinology"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"632","DOI":"10.1111\/bjd.15651","article-title":"Paracrine regulation of melanogenesis","volume":"178","author":"Yuan","year":"2018","journal-title":"Br. 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