Laser capture microdissection followed by next-generation sequencing identifies disease-related microRNAs in psoriatic skin that reflect systemic microRNA changes in psoriasis

被引:94
作者
Lovendorf, Marianne B. [1 ,2 ]
Mitsui, Hiroshi [3 ]
Zibert, John R. [2 ]
Ropke, Mads A. [2 ]
Hafner, Markus [4 ]
Dyring-Andersen, Beatrice [1 ,5 ]
Bonefeld, Charlotte M. [5 ]
Krueger, James G. [3 ]
Skov, Lone [1 ]
机构
[1] Univ Copenhagen, Gentofte Hosp, Dept Dermatoallergol, DK-2900 Hellerup, Denmark
[2] LEO Pharma AS, Ballerup, Denmark
[3] Rockefeller Univ, Lab Invest Dermatol, New York, NY 10021 USA
[4] Rockefeller Univ, Howard Hughes Med Inst, Lab RNA Mol Biol, New York, NY 10021 USA
[5] Univ Copenhagen, Dept Int Hlth Immunol & Microbiol, DK-2900 Hellerup, Denmark
关键词
laser capture microdissection; microRNAs; next-generation sequencing; psoriasis; skin; T-CELLS; GENE-EXPRESSION; RNAS; PROLIFERATION; PATHOGENESIS; REGULATORS; AXIS;
D O I
10.1111/exd.12604
中图分类号
R75 [皮肤病学与性病学];
学科分类号
100227 [皮肤病学];
摘要
Psoriasis is a systemic disease with cutaneous manifestations. MicroRNAs (miRNAs) are small non-coding RNA molecules that are differentially expressed in psoriatic skin; however, only few cell-and region-specific miRNAs have been identified in psoriatic lesions. We used laser capture microdissection (LCM) and next-generation sequencing (NGS) to study the specific miRNA expression profiles in the epidermis (Epi) and dermal inflammatory infiltrates (RD) of psoriatic skin (N = 6). We identified 24 deregulated miRNAs in the Epi and 37 deregulated miRNAs in the RD of psoriatic plaque compared with normal psoriatic skin (FCH > 2, FDR < 0.05). Interestingly, 9 of the 37 miRNAs in RD, including miR-193b and miR-223, were recently described as deregulated in circulating peripheral blood mononuclear cells (PBMCs) from patients with psoriasis. Using flow cytometry and qRT-PCR, we found that miR-193b and miR-223 were expressed in Th17 cells. In conclusion, we demonstrate that LCM combined with NGS provides a robust approach to explore the global miRNA expression in the epidermal and dermal compartments of psoriatic skin. Furthermore, our results indicate that the altered local miRNA changes seen in the RD are reflected in the circulating immune cells, suggesting that miRNAs may contribute to the pathogenesis of psoriasis.
引用
收藏
页码:187 / 193
页数:7
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