{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T13:09:01Z","timestamp":1790168941115,"version":"4.1.0"},"reference-count":30,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2020,3,2]],"date-time":"2020-03-02T00:00:00Z","timestamp":1583107200000},"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>Riehl\u2019s melanosis is a hyperpigmentary disorder that occurs predominantly on the face and neck. To date, the pathogenesis of Riehl\u2019s melanosis with regards to the melanogenic properties and paracrine melanogenic molecules has not well been studied. This study was aimed to provide a novel perspective on the pathogenesis of Riehl\u2019s melanosis by identifying the relevant paracrine melanogenic molecules in Riehl\u2019s melanosis. Skin biopsies were performed on lesional and normal-appearing perilesional skin of 12 patients with Riehl\u2019s melanosis and 12 age- and sex-matched healthy controls. Histopathological and immunohistochemical staining for paracrine melanogenic molecules was analyzed. The major histopathological findings of Riehl\u2019s melanosis were basal hyperpigmentation, melanocyte proliferation, interface change, dermal pigmentary incontinence, vascular proliferation, and dermal inflammation. Dermal expression intensities of stem cell factor (SCF) and c-kit were increased in the lesional skin of Riehl\u2019s melanosis. In addition, increased expression of epidermal and dermal ET-1 was also observed in the lesional skin of Riehl\u2019s melanosis. Increased tissue expressions of SCF, c-kit, and ET-1 in Riehl\u2019s melanosis support the role of these paracrine melanogenic molecules in the pathogenesis of Riehl\u2019s melanosis. The findings from this study might present useful information on the pathogenetic mechanism of Riehl\u2019s melanosis.<\/jats:p>","DOI":"10.3390\/ijms21051695","type":"journal-article","created":{"date-parts":[[2020,3,3]],"date-time":"2020-03-03T03:13:28Z","timestamp":1583205208000},"page":"1695","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Melanogenic Properties and Expression Profiles of Melanogenic Paracrine Molecules in Riehl\u2019s Melanosis"],"prefix":"10.3390","volume":"21","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2903-9534","authenticated-orcid":false,"given":"Yu","family":"Woo","sequence":"first","affiliation":[{"name":"Department of Dermatology, Incheon St. Mary\u2019s Hospital, College of Medicine, The Catholic University of Korea, Incheon 21431, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hyo","family":"Park","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Yeouido St. Mary\u2019s Hospital, College of Medicine, The Catholic University of Korea, Seoul 07345, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seo-Won","family":"Jeong","sequence":"additional","affiliation":[{"name":"Institute of Clinical Medical Research, Yeouido St. Mary\u2019s Hospital, College of Medicine, The Catholic University of Korea, Seoul 07345, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hyun","family":"Park","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Yeouido St. Mary\u2019s Hospital, College of Medicine, The Catholic University of Korea, Seoul 07345, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,3,2]]},"reference":[{"key":"ref_1","first-page":"780","article-title":"\u00dcber eine eigenartige Melanose","volume":"25","author":"Riehl","year":"1917","journal-title":"Wien. Klin Wochschr"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"644","DOI":"10.1684\/ejd.2018.3404","article-title":"Acquired diffuse slate-grey facial dyspigmentation due to henna: An unrecognized cause of pigment contact dermatitis in Korean patients","volume":"28","author":"Woo","year":"2018","journal-title":"Eur. J. Dermatol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1111\/j.1600-0536.1999.tb06014.x","article-title":"Screening patch tests for pigmented contact dermatitis in Israel","volume":"40","author":"Trattner","year":"1999","journal-title":"Contact Dermat."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"263","DOI":"10.1111\/ijd.14189","article-title":"A global consensus statement on ashy dermatosis, erythema dyschromicum perstans, lichen planus pigmentosus, idiopathic eruptive macular pigmentation, and Riehl\u2019s melanosis","volume":"58","author":"Kumarasinghe","year":"2019","journal-title":"Int. J. Derm."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1080\/09546634.2016.1187706","article-title":"A pilot study for triple combination therapy with a low-fluence 1064 nm Q-switched Nd:YAG laser, hydroquinone cream and oral tranexamic acid for recalcitrant Riehl\u2019s Melanosis","volume":"28","author":"Kwon","year":"2017","journal-title":"J. Dermatol. Treat."},{"key":"ref_6","first-page":"119","article-title":"A pilot study of intense pulsed light in the treatment of Riehl\u2019s melanosis","volume":"37","author":"Li","year":"2011","journal-title":"Dermatol. Surg. Off. Publ. Am. Soc. Dermatol. Surg."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1199","DOI":"10.1111\/jdv.12264","article-title":"Four views of Riehl\u2019s melanosis: Clinical appearance, dermoscopy, confocal microscopy and histopathology","volume":"28","author":"Wang","year":"2014","journal-title":"J. Eur. Acad. Dermatol. Venereol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"18352","DOI":"10.1016\/S0021-9258(18)55277-7","article-title":"Effects of endothelins on signal transduction and proliferation in human melanocytes","volume":"266","author":"Yada","year":"1991","journal-title":"J. Biol. Chem."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"578","DOI":"10.1046\/j.1523-1747.2001.01290.x","article-title":"The paracrine role of stem cell factor\/c-kit signaling in the activation of human melanocytes in ultraviolet-B-induced pigmentation","volume":"116","author":"Hachiya","year":"2001","journal-title":"J. Invest. Derm."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"625","DOI":"10.1042\/bj3130625","article-title":"Granulocyte\/macrophage colony-stimulating factor is an intrinsic keratinocyte-derived growth factor for human melanocytes in UVA-induced melanosis","volume":"313","author":"Imokawa","year":"1996","journal-title":"Biochem. J."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"2258","DOI":"10.1172\/JCI117224","article-title":"Proopiomelanocortin-derived peptides are synthesized and released by human keratinocytes","volume":"93","author":"Schauer","year":"1994","journal-title":"J. Clin. Investig."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1111\/j.1365-2133.2006.07210.x","article-title":"Alterations in the epidermal-dermal melanin axis and factor XIIIa melanophages in senile lentigo and ageing skin","volume":"155","author":"Unver","year":"2006","journal-title":"Br. J. Dermatol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"266","DOI":"10.1111\/j.1600-0560.1989.tb00050.x","article-title":"Factor XIIIa is expressed by fibroblasts in fibrovascular tumors","volume":"16","author":"Nemeth","year":"1989","journal-title":"J. Cutan. Pathol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"3571861","DOI":"10.1155\/2017\/3571861","article-title":"Factor XIII Subunit A in the Skin: Applications in Diagnosis and Treatment","volume":"2017","author":"Paragh","year":"2017","journal-title":"Biomed. Res. Int."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"e105","DOI":"10.1111\/j.1468-3083.2012.04556.x","article-title":"Dermal dendrocytes FXIIIA+ phagocytizing extruded mast cell granules in drug-induced acute urticaria","volume":"27","author":"Criado","year":"2013","journal-title":"J. Eur. Acad. Dermatol. Venereol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"2225","DOI":"10.1038\/jid.2008.56","article-title":"\u201cDermal dendritic cells\u201d comprise two distinct populations: CD1+ dendritic cells and CD209+ macrophages","volume":"128","author":"Ochoa","year":"2008","journal-title":"J Invest. Derm."},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Li, P.H., Liu, L.H., Chang, C.C., Gao, R., Leung, C.H., Ma, D.L., and David Wang, H.M. (2018). Silencing Stem Cell Factor Gene in Fibroblasts to Regulate Paracrine Factor Productions and Enhance c-Kit Expression in Melanocytes on Melanogenesis. Int. J. Mol. Sci., 19.","DOI":"10.3390\/ijms19051475"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"4235","DOI":"10.1038\/s41598-018-22608-y","article-title":"Ultraviolet-irradiated endothelial cells secrete stem cell factor and induce epidermal pigmentation","volume":"8","author":"Kim","year":"2018","journal-title":"Sci. Rep."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"106","DOI":"10.1016\/S0923-1811(00)00164-X","article-title":"Role of stem cell factor and monocyte chemoattractant protein-1 in the interaction between fibroblasts and mast cells in fibrosis","volume":"26","author":"Yamamoto","year":"2001","journal-title":"J. Dermatol. Sci."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"327","DOI":"10.1016\/j.ejphar.2005.12.067","article-title":"Stem cell factor and its receptor c-Kit as targets for inflammatory diseases","volume":"533","author":"Reber","year":"2006","journal-title":"Eur. J. Pharmacol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"78","DOI":"10.1007\/BF00370723","article-title":"Stem cell factor, a novel cutaneous growth factor for mast cells and melanocytes","volume":"287","author":"Grabbe","year":"1994","journal-title":"Arch. Dermatol. Res."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1302","DOI":"10.1056\/NEJM199305063281803","article-title":"Altered metabolism of mast-cell growth factor (c-kit ligand) in cutaneous mastocytosis","volume":"328","author":"Morganroth","year":"1993","journal-title":"N. Engl. J. Med."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"571","DOI":"10.1046\/j.1523-1747.2001.01296.x","article-title":"The role of the epidermal endothelin cascade in the hyperpigmentation mechanism of lentigo senilis","volume":"116","author":"Kadono","year":"2001","journal-title":"J. Investig. Dermatol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"485","DOI":"10.1007\/s004280000362","article-title":"Expression of the endothelin-B receptor in pigment cell lesions of the skin. Evidence for its role as tumor progression marker in malignant melanoma","volume":"438","author":"Demunter","year":"2001","journal-title":"Virchows Arch."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"3911","DOI":"10.1242\/dev.122.12.3911","article-title":"Multiple roles for endothelin in melanocyte development: Regulation of progenitor number and stimulation of differentiation","volume":"122","author":"Reid","year":"1996","journal-title":"Development"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"355","DOI":"10.1093\/hmg\/5.3.355","article-title":"Heterozygous endothelin receptor B (EDNRB) mutations in isolated Hirschsprung disease","volume":"5","author":"Amiel","year":"1996","journal-title":"Hum. Mol. Genet."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"918","DOI":"10.1046\/j.1365-2133.1996.d01-1095.x","article-title":"Role of endothelin-1 in hyperpigmentation in seborrhoeic keratosis","volume":"135","author":"Teraki","year":"1996","journal-title":"Br. J. Dermatol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1115","DOI":"10.1038\/labinvest.3700469","article-title":"Interaction between stem cell factor and endothelin-1: Effects on melanogenesis in human skin xenografts","volume":"86","author":"Sriwiriyanont","year":"2006","journal-title":"Lab. Investig."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"680","DOI":"10.1111\/exd.12745","article-title":"Recombinant erythroid differentiation regulator 1 inhibits both inflammation and angiogenesis in a mouse model of rosacea","volume":"24","author":"Kim","year":"2015","journal-title":"Exp. Dermatol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"3798","DOI":"10.1200\/JCO.2003.11.069","article-title":"Epidermal growth factor receptor in non\u2013small-cell lung carcinomas: Correlation between gene copy number and protein expression and impact on prognosis","volume":"21","author":"Hirsch","year":"2003","journal-title":"J. Clin. Oncol."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/21\/5\/1695\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T09:03:09Z","timestamp":1760173389000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/21\/5\/1695"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,3,2]]},"references-count":30,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2020,3]]}},"alternative-id":["ijms21051695"],"URL":"https:\/\/doi.org\/10.3390\/ijms21051695","relation":{"has-review":[{"id-type":"doi","id":"10.3410\/f.737477429.793578857","asserted-by":"object"}]},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,3,2]]}}}