title: Transcriptional profiling shows altered expression of wnt pathway- and lipid metabolism-related genes as well as melanogenesis-related genes in melasma.
abstract: Melasma is a commonly acquired hyperpigmentary disorder of the face, but its pathogenesis is poorly understood and its treatment remains challenging. We conducted a comparative histological study on lesional and perilesional normal skin to clarify the histological nature of melasma. Significantly, higher amounts of melanin and of melanogenesis-associated proteins were observed in the epidermis of lesional skin, and the mRNA level of tyrosinase-related protein 1 was higher in lesional skin, indicating regulation at the mRNA level. However, melanocyte numbers were comparable between lesional and perilesional skin. A transcriptomic study was undertaken to identify genes involved in the pathology of melasma. A total of 279 genes were found to be differentially expressed in lesional and perilesional skin. As was expected, the mRNA levels of a number of known melanogenesis-associated genes, such as tyrosinase, were found to be elevated in lesional skin. Bioinformatics analysis revealed that the most lipid metabolism-associated genes were downregulated in lesional skin, and this finding was supported by an impaired barrier function in melasma. Interestingly, a subset of Wnt signaling modulators, including Wnt inhibitory factor 1, secreted frizzled-related protein 2, and Wnt5a, were also found to be upregulated in lesional skin. Immunohistochemistry confirmed the higher expression of these factors in melasma lesions.
authors.affiliation: Department of Dermatology, Ajou University School of Medicine, Suwon, Korea.
authors.forename: Hee Young
authors.initials: HY
authors.lastname: Kang
authors.forename: Itaru
authors.initials: I
authors.lastname: Suzuki
authors.forename: Dong Jun
authors.initials: DJ
authors.lastname: Lee
authors.forename: Jaehyun
authors.initials: J
authors.lastname: Ha
authors.forename: Pascale
authors.initials: P
authors.lastname: Reiniche
authors.forename: Jérôme
authors.initials: J
authors.lastname: Aubert
authors.forename: Sophie
authors.initials: S
authors.lastname: Deret
authors.forename: Didier
authors.initials: D
authors.lastname: Zugaj
authors.forename: Johannes J
authors.initials: JJ
authors.lastname: Voegel
authors.forename: Jean-Paul
authors.initials: JP
authors.lastname: Ortonne
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism; D000328:Adult; D051157:Frizzled Receptors / Q000235:genetics / Q000378:metabolism; D020869:Gene Expression Profiling; D006801:Humans; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D050356:Lipid Metabolism / Q000235:genetics*; D008544:Melanocytes / Q000502:physiology; D008548:Melanosis / Q000235:genetics* / Q000378:metabolism* / Q000473:pathology; D008562:Membrane Glycoproteins / Q000235:genetics / Q000378:metabolism; D008875:Middle Aged; D010088:Oxidoreductases / Q000235:genetics / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism; D043562:Receptors, G-Protein-Coupled / Q000235:genetics / Q000378:metabolism; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism; D051153:Wnt Proteins / Q000235:genetics* / Q000378:metabolism*; D000071818:Wnt-5a Protein; D051155:Wnt1 Protein / Q000235:genetics / Q000378:metabolism
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C489742:FZD2 protein, human; D051157:Frizzled Receptors; D008562:Membrane Glycoproteins; D011518:Proto-Oncogene Proteins; D043562:Receptors, G-Protein-Coupled; D012097:Repressor Proteins; C485569:WIF1 protein, human; C085389:WNT5A protein, human; D051153:Wnt Proteins; D000071818:Wnt-5a Protein; D051155:Wnt1 Protein; D010088:Oxidoreductases; C489799:TYRP1 protein, human