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

Summary 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 dela...

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Veröffentlicht in:British journal of dermatology (1951) 2007-06, Vol.156 (6), p.1214-1223
Hauptverfasser: Aoki, H., Moro, O., Tagami, H., Kishimoto, J.
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creator Aoki, H.
Moro, O.
Tagami, H.
Kishimoto, J.
description Summary 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. Objectives  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 pr
doi_str_mv 10.1111/j.1365-2133.2007.07830.x
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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. Objectives  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.</description><identifier>ISSN: 0007-0963</identifier><identifier>EISSN: 1365-2133</identifier><identifier>DOI: 10.1111/j.1365-2133.2007.07830.x</identifier><identifier>PMID: 17419692</identifier><identifier>CODEN: BJDEAZ</identifier><language>eng</language><publisher>Oxford, UK: Blackwell Publishing Ltd</publisher><subject>Adult ; Biological and medical sciences ; Dermatology ; Gene Expression Profiling - methods ; Humans ; Immunohistochemistry - methods ; keratinocytes ; Keratinocytes - metabolism ; Lentigo ; Lentigo - genetics ; Male ; Medical sciences ; Melanins - analysis ; Melanins - genetics ; melanocyte ; microarray ; Middle Aged ; senile lentigo ; skin ; Skin - metabolism ; Skin - radiation effects ; Skin Aging - genetics ; Skin Aging - physiology ; solar lentigo ; Tumors of the skin and soft tissue. Premalignant lesions ; Ultraviolet Rays - adverse effects</subject><ispartof>British journal of dermatology (1951), 2007-06, Vol.156 (6), p.1214-1223</ispartof><rights>2007 The Authors. 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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. Objectives  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.</description><subject>Adult</subject><subject>Biological and medical sciences</subject><subject>Dermatology</subject><subject>Gene Expression Profiling - methods</subject><subject>Humans</subject><subject>Immunohistochemistry - methods</subject><subject>keratinocytes</subject><subject>Keratinocytes - metabolism</subject><subject>Lentigo</subject><subject>Lentigo - genetics</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Melanins - analysis</subject><subject>Melanins - genetics</subject><subject>melanocyte</subject><subject>microarray</subject><subject>Middle Aged</subject><subject>senile lentigo</subject><subject>skin</subject><subject>Skin - metabolism</subject><subject>Skin - radiation effects</subject><subject>Skin Aging - genetics</subject><subject>Skin Aging - physiology</subject><subject>solar lentigo</subject><subject>Tumors of the skin and soft tissue. Premalignant lesions</subject><subject>Ultraviolet Rays - adverse effects</subject><issn>0007-0963</issn><issn>1365-2133</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2007</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqNkE9v0zAYhy0EYt3gKyBf4JbwOm7s5MCBDVo2VRsSII6W47xeXZyk2Klov_2ctdqu-OI_7_N7bT-EUAY5S-PjJmdclFnBOM8LAJmDrDjk-xdk9lR4SWaQShnUgp-R8xg3AIxDCa_JGZNzVou6mBG7xB4p7rcBY3RDT7dhsM67_p7qXvtDdJEOlsbB60A99qO7H6jraUCvx4kf07brdv2wdnEczBo7Z7SnZq2DNiOGdOpMfENeWe0jvj3NF-TX4uvPq2_Z6m55ffV5lZmSF5CJUs4FMDBNYxoOKGusZFtUVVEZXbOal01phRWmZRwrwVuwMIeigpbNayYtvyAfjn3TN_7uMI6qc9Gg97rHYRdVkjVZEAmsjqAJQ4wBrdoG1-lwUAzU5Fht1KRSTSqnmFSPjtU-Rd-d7tg1HbbPwZPUBLw_ATomFzbo3rj4zFVSCMlk4j4duX_O4-G_H6Aub75Mq5TPjvnkGPdPeR3-KCG5LNXv26W6ET_YYvF9pS75A6UXp64</recordid><startdate>200706</startdate><enddate>200706</enddate><creator>Aoki, H.</creator><creator>Moro, O.</creator><creator>Tagami, H.</creator><creator>Kishimoto, J.</creator><general>Blackwell Publishing Ltd</general><general>Blackwell</general><scope>BSCLL</scope><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>8FD</scope><scope>FR3</scope><scope>P64</scope><scope>RC3</scope></search><sort><creationdate>200706</creationdate><title>Gene expression profiling analysis of solar lentigo in relation to immunohistochemical characteristics</title><author>Aoki, H. ; Moro, O. ; Tagami, H. ; Kishimoto, J.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c5320-65746010cbbcb30e79e87d28828ca91935b5f6f6cd13e863d0f040280d14917f3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2007</creationdate><topic>Adult</topic><topic>Biological and medical sciences</topic><topic>Dermatology</topic><topic>Gene Expression Profiling - methods</topic><topic>Humans</topic><topic>Immunohistochemistry - methods</topic><topic>keratinocytes</topic><topic>Keratinocytes - metabolism</topic><topic>Lentigo</topic><topic>Lentigo - genetics</topic><topic>Male</topic><topic>Medical sciences</topic><topic>Melanins - analysis</topic><topic>Melanins - genetics</topic><topic>melanocyte</topic><topic>microarray</topic><topic>Middle Aged</topic><topic>senile lentigo</topic><topic>skin</topic><topic>Skin - metabolism</topic><topic>Skin - radiation effects</topic><topic>Skin Aging - genetics</topic><topic>Skin Aging - physiology</topic><topic>solar lentigo</topic><topic>Tumors of the skin and soft tissue. Premalignant lesions</topic><topic>Ultraviolet Rays - adverse effects</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Aoki, H.</creatorcontrib><creatorcontrib>Moro, O.</creatorcontrib><creatorcontrib>Tagami, H.</creatorcontrib><creatorcontrib>Kishimoto, J.</creatorcontrib><collection>Istex</collection><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Technology Research Database</collection><collection>Engineering Research Database</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Genetics Abstracts</collection><jtitle>British journal of dermatology (1951)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Aoki, H.</au><au>Moro, O.</au><au>Tagami, H.</au><au>Kishimoto, J.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Gene expression profiling analysis of solar lentigo in relation to immunohistochemical characteristics</atitle><jtitle>British journal of dermatology (1951)</jtitle><addtitle>Br J Dermatol</addtitle><date>2007-06</date><risdate>2007</risdate><volume>156</volume><issue>6</issue><spage>1214</spage><epage>1223</epage><pages>1214-1223</pages><issn>0007-0963</issn><eissn>1365-2133</eissn><coden>BJDEAZ</coden><abstract>Summary 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. Objectives  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.</abstract><cop>Oxford, UK</cop><pub>Blackwell Publishing Ltd</pub><pmid>17419692</pmid><doi>10.1111/j.1365-2133.2007.07830.x</doi><tpages>10</tpages></addata></record>
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source Oxford University Press Journals All Titles (1996-Current); Wiley Online Library - AutoHoldings Journals; MEDLINE
subjects Adult
Biological and medical sciences
Dermatology
Gene Expression Profiling - methods
Humans
Immunohistochemistry - methods
keratinocytes
Keratinocytes - metabolism
Lentigo
Lentigo - genetics
Male
Medical sciences
Melanins - analysis
Melanins - genetics
melanocyte
microarray
Middle Aged
senile lentigo
skin
Skin - metabolism
Skin - radiation effects
Skin Aging - genetics
Skin Aging - physiology
solar lentigo
Tumors of the skin and soft tissue. Premalignant lesions
Ultraviolet Rays - adverse effects
title Gene expression profiling analysis of solar lentigo in relation to immunohistochemical characteristics
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