Aoki H, Moro O, Tagami H, Kishimoto J
Shiseido Research Center, 2-12-2 Fukuura, Kanazawa-ku, Yokohama-shi, Kanagawa 236-8643, Japan.
Br J Dermatol. 2007 Jun;156(6):1214-23. doi: 10.1111/j.1365-2133.2007.07830.x. Epub 2007 Apr 5.
Solar lentigo appears as dark brown spots that occur on sun-exposed areas and is considered to be a hallmark of aged skin. Although considerable knowledge about acute pigmentation has recently been accumulated, little is yet known about the mechanisms underlying chronic- and delayed-type hyperpigmentation, such as solar lentigo.
To clarify further the mechanisms underlying the development of solar lentigo, we carried out gene expression analysis in skin biopsy specimens obtained from human solar lentigines using DNA microarray analysis.
Two pairs of skin specimens were obtained from solar lentigo and adjacent sun-exposed normal skin, as well as normal skin on the buttocks of 16 volunteers aged 40-55 years. One set of specimens was frozen and RNA was extracted for microarray and the other set was prepared for histological sections and analysed by antibodies and probes.
Sixty-five genes were upregulated more than 1.8-fold in solar lentigo compared with adjacent control skin and seven melanocyte-related genes were included. Compared with sun-protected skin, many inflammation-related genes were upregulated in solar lentigo, and compared with sun-exposed control skin, upregulation of genes related to fatty-acid metabolism was apparent in solar lentigo. Moreover, we found downregulation of cornified envelope-related genes, which suggests suppression of cornification in the epidermis in solar lentigo. Immunohistochemically, larger numbers of TRP1-positive cells were found in the basal layer of solar lentigo than in normal skin. Fatty acid-related genes were highly expressed in the epidermis as detected by in situ hybridization, and they were much more prominent in the lesional skin of solar lentigo. However, cycling epidermal cells detectable with Ki67 antibody were fewer in the lesional skin of solar lentigo. Expression of filaggrin and involucrin was decreased in the lesional skin, where the number of cell layers of the stratum corneum was significantly higher than in normal skin.
The results of the present microarray analysis of solar lentigo, demonstrating upregulation of genes related to inflammation, fatty-acid metabolism and melanocytes and downregulation of cornified envelope-related genes, suggest that solar lentigo is induced by the mutagenic effect of repeated ultraviolet light exposures in the past, leading to the characteristic enhancement of melanin production, together with decreased proliferation and differentiation of lesional keratinocytes on the background of chronic inflammation.
日光性雀斑表现为出现在阳光暴露部位的深褐色斑点，被认为是皮肤老化的一个标志。尽管最近已经积累了大量关于急性色素沉着的知识，但对于慢性和迟发型色素沉着（如日光性雀斑）的潜在机制仍知之甚少。
为了进一步阐明日光性雀斑发生发展的机制，我们使用DNA微阵列分析对取自人类日光性雀斑的皮肤活检标本进行了基因表达分析。
从日光性雀斑及相邻的阳光暴露正常皮肤，以及16名40 - 55岁志愿者臀部的正常皮肤获取两对皮肤标本。一组标本冷冻后提取RNA用于微阵列分析，另一组标本制备组织切片并通过抗体和探针进行分析。
与相邻对照皮肤相比，日光性雀斑中有65个基因上调超过1.8倍，其中包括7个与黑素细胞相关的基因。与防晒皮肤相比，日光性雀斑中有许多炎症相关基因上调，与阳光暴露对照皮肤相比，日光性雀斑中脂肪酸代谢相关基因上调明显。此外，我们发现角质包膜相关基因下调，这表明日光性雀斑表皮中的角质化受到抑制。免疫组织化学显示，日光性雀斑基底层中TRP1阳性细胞数量比正常皮肤多。通过原位杂交检测发现，脂肪酸相关基因在表皮中高表达，且在日光性雀斑的皮损皮肤中更为突出。然而，用Ki67抗体可检测到的循环表皮细胞在日光性雀斑的皮损皮肤中较少。在皮损皮肤中，丝聚蛋白和兜甲蛋白的表达降低，此处角质层细胞层数明显高于正常皮肤。
本次对日光性雀斑的微阵列分析结果表明，炎症、脂肪酸代谢和黑素细胞相关基因上调，角质包膜相关基因下调，提示日光性雀斑是过去反复紫外线照射的诱变作用所致，导致黑素生成特征性增强，同时在慢性炎症背景下皮损角质形成细胞的增殖和分化减少。
