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.

Melanocytes and Their Diseases

“…Bioinformatics studies have shown that genes responsible for melasma include Wnt and lipid metabolism-related genes in addition to melanogenic markers (Kang et al 2011) and that reduced expression levels of WIF-1 (Wnt inhibitory factor-1) in keratinocytes and/or fibroblasts may play roles in the development of melasma (Kim et al 2013). Patients with mastocytosis usually carry the D816 V KIT mutation and a bioinformatics study shows that those patients show the up-regulation of genes involved in innate and inflammatory immune responses, including interferon-induced genes and genes involved in cellular responses to viral antigens, together with complement inhibitory molecules and genes involved in lipid metabolism and protein processing.…”

Gene Expression Profiling in Melasma in Korean Women

“…Yet there is a paucity of data about the difference in the degree of mRNA transcription of the above genes between melasma lesional skin and normal adjacent one. There was only one previous transcriptomic study in this series: Kang et al [9] reported that there was up-regulation of genes involved in the melanogenesis and Wnt signaling and down-regulation of those involved in the lipid metabolism in melasma lesional skin compared with normal adjacent one. In addition, it has also been reported that H19 gene and Wnt inhibitory factor-1 (WIF-1) are down-regulated and PDZ domain protein kidney 1 (PDZK1) is up-regulated in melasma lesional skin [10,11,12].…”

THE DUAL TONING TECHNIQUE FOR MELASMA TREATMENT WITH THE 1064 nm Nd: YAG LASER: A PRELIMINARY STUDY

“…[1][2][3][4] More recently, the molecular signaling mechanisms responsible for upregulating and downregulating the genetic pathways leading to hypermelanogenesis have been identified including the Wnt pathway, c-kit and the role of dermal stem cells, although what actually triggers the respective signaling process remains to be elucidated. 5,6) A large variety of topical therapeutic approaches has been reported including bleaching agents (hydroquinone and kojic acids) and chemical peels (retinol, trichloroacetic or kojic acid), but although some success has been reported with these, the results are somewhat inconsistent with undesirable side effects such as unwanted pigmentary changes and dermatitis, 7) and their efficacy appears to decrease with long-term use. In the past few years, intense pulsed light (IPL) systems have been reported in the treatment of mild melasma in the Japanese skin, 8) and pigment-selective visible light lasers, but the results were less than expected with side effects related to excess photothermal damage to the epidermis and dermis associated with these systems, particularly post-inflammatory secondary hyperpigmentation (PIH).…”