Transcriptional profiling shows altered expression of wnt pathway- and lipid metabolism-related genes as well as melanogenesis-related genes in melasma.. Homo sapiens

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. Overall design: Total of 48 chips. 12 patients : 2 biospies per patient: 1 lesional and 1 non lesional: 1 technical replicate per chip

黄褐斑（melasma）是一种常见的获得性面部色素沉着性疾病，但其发病机制尚不明确，治疗仍颇具挑战。本研究针对皮损及皮损周围正常皮肤开展对比组织学研究，以阐明黄褐斑的组织学本质。研究发现，皮损表皮内的黑色素及黑色素生成相关蛋白含量显著更高，且皮损组织中酪氨酸酶相关蛋白1（tyrosinase-related protein 1）的mRNA水平更高，提示该调控过程发生于mRNA层面。不过，皮损与皮损周围皮肤的黑素细胞数量并无显著差异。为筛选参与黄褐斑病理过程的基因，本研究开展了转录组学分析，最终共鉴定出279个在皮损与皮损周围皮肤中差异表达的基因。正如预期，多个已知的黑色素生成相关基因（如酪氨酸酶（tyrosinase））的mRNA水平在皮损组织中均呈上调趋势。生物信息学分析显示，多数与脂质代谢相关的基因在皮损组织中呈下调表达，这一发现也得到了黄褐斑患者皮肤屏障功能受损的研究结果佐证。值得注意的是，一组Wnt信号通路调控因子——包括Wnt抑制因子1（Wnt inhibitory factor 1）、分泌型卷曲相关蛋白2（secreted frizzled-related protein 2）以及Wnt5a——在皮损组织中也呈现上调表达，免疫组化实验进一步证实了这些因子在黄褐斑皮损中的高表达。总体实验设计：共使用48张芯片。纳入12名患者，每名患者采集2份活检样本：1份皮损组织样本与1份非皮损组织样本；每张芯片设置1次技术重复（technical replicate）。