Combined use of laser capture microdissection and cDNA microarray analysis identifies locally expressed disease-related genes in focal regions of psoriasis vulgaris skin lesions

激光捕获显微切割和cDNA微阵列分析相结合,可识别寻常型银屑病皮损局灶区域中局部表达的疾病相关基因。

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作者:Hiroshi Mitsui ,Mayte Suárez-Fariñas, Daniel A Belkin, Natasha Levenkova, Judilyn Fuentes-Duculan, Israel Coats, Hideki Fujita, James G Krueger

Abstract

Psoriasis vulgaris is a complex disease characterized by alterations in growth and differentiation of epidermal keratinocytes, as well as a marked increase in leukocyte populations. Lesions are known to contain alterations in messenger RNAs encoding more than 1,000 products, but only a very small number of these transcripts has been localized to specific cell types or skin regions. In this study, we used laser capture microdissection (LCM) and gene array analysis to study the gene expression of cells in lesional epidermis (EPI) and dermis, compared with the corresponding non-lesional regions. Using this approach, we detected >1,800 differentially expressed gene products in the EPI or dermis of psoriasis lesions. These results established sets of genes that are differentially expressed between epidermal and dermal compartments, as well as between non-lesional and lesional psoriasis skin. One of our findings involved the local production of CCL19, a lymphoid-organizing chemokine, and its receptor CCR7 in psoriatic dermal aggregates, along with the presence of gene products LAMP3/DC-LAMP and CD83, which typify mature dendritic cells (DCs). Gene expression patterns obtained with LCM and microarray analysis along with T-cell and DC detection by immune staining suggest a possible mechanism for lymphoid organization via CCL19/CCR7 in diseased skin.

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