title: Laser capture microdissection followed by next-generation sequencing identifies disease-related microRNAs in psoriatic skin that reflect systemic microRNA changes in psoriasis.
abstract: 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.
authors.affiliation: Department of Dermato-Allergology, Gentofte Hospital, University of Copenhagen, Hellerup, Denmark; LEO Pharma A/S, Ballerup, Denmark.
authors.forename: Marianne B
authors.initials: MB
authors.lastname: Løvendorf
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Mitsui
authors.forename: John R
authors.initials: JR
authors.lastname: Zibert
authors.forename: Mads A
authors.initials: MA
authors.lastname: Røpke
authors.forename: Markus
authors.initials: M
authors.lastname: Hafner
authors.forename: Beatrice
authors.initials: B
authors.lastname: Dyring-Andersen
authors.forename: Charlotte M
authors.initials: CM
authors.lastname: Bonefeld
authors.forename: James G
authors.initials: JG
authors.lastname: Krueger
authors.forename: Lone
authors.initials: L
authors.lastname: Skov
mesh_terms: D020405:Dermis / Q000737:chemistry; D004817:Epidermis / Q000737:chemistry*; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D006801:Humans; D007249:Inflammation / Q000235:genetics*; D061346:Laser Capture Microdissection; D035683:MicroRNAs / Q000032:analysis* / Q000235:genetics; D011565:Psoriasis / Q000235:genetics*; D017423:Sequence Analysis, RNA; D058504:Th17 Cells / Q000737:chemistry*
chemical_list: D035683:MicroRNAs; C546818:MIRN193 microRNA, human; C525067:MIR223, human
keywords: laser capture microdissection; microRNAs; next-generation sequencing; psoriasis; skin