Gene expression profiling analysis of solar lentigo in relation to immunohistochemical characteristics.
BACKGROUND
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.


OBJECTIVE
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.


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
Aoki
H
H
Shiseido Research Center, 2-12-2 Fukuura, Kanazawa-ku, Yokohama-shi, Kanagawa 236-8643, Japan. hirofumi.aoki@to.shiseido.co.jp
Moro
O
O
Tagami
H
H
Kishimoto
J
J
D000328:Adult; D000091344:Filaggrin Proteins; D020869:Gene Expression Profiling / Q000379:methods*; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D015603:Keratinocytes / Q000378:metabolism*; D007911:Lentigo / Q000235:genetics*; D008297:Male; D008543:Melanins / Q000032:analysis* / Q000235:genetics; D008875:Middle Aged; D012867:Skin / Q000378:metabolism / Q000528:radiation effects*; D015595:Skin Aging / Q000235:genetics* / Q000502:physiology; D014466:Ultraviolet Rays / Q000009:adverse effects*
C000717249:FLG protein, human; D000091344:Filaggrin Proteins; D008543:Melanins