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

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 microdissectio...

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Published inExperimental dermatology Vol. 24; no. 3; pp. 187 - 193
Main Authors Løvendorf, Marianne B., Mitsui, Hiroshi, Zibert, John R., Røpke, Mads A., Hafner, Markus, Dyring-Andersen, Beatrice, Bonefeld, Charlotte M., Krueger, James G., Skov, Lone
Format Journal Article
LanguageEnglish
Published Denmark Blackwell Publishing Ltd 01.03.2015
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Summary: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.
Bibliography:ark:/67375/WNG-0SGM4DC5-R
Pfizer
Ministry of Science, Innovation and Higher education, Denmark
istex:5D0BAD216EC0943814C35C311367876E23B1B895
ArticleID:EXD12604
Figure S1. Abundantly expressed miRNAs in psoriatic skin. Figure S2. Epidermal psoriatic miRNA signature. Figure S3. Validation of epidermal psoriatic deregulated miRNAs. Figure S4. Dermal psoriatic miRNA signature. Figure S5. MicroRNA expression in T cell subsets. Figure S6. Overlap between deregulated miRNAs in psoriatic plaque epidermis (PPEpi), psoriatic plaque dermal inflammatory infiltrates (PPRD) and whole tissue extracts. Table S1. (a) Patient Demographic. (b) Patient Demographics. Table S2. Significant altered miRNAs between Epi and RD in normal psoriatic skin. Table S3. Overlapping deregulated miRNAs between PPRD and PBMCs from patients with psoriasis. Table S4. Deregulated miRNAs in T cell subsets. Table S5. Significantly deregulated miRNAs in psoriatic plaque versus normal psoriatic skin (whole tissue extract). Table S6. Experimental design. Table S7. Target predictions for the epidermal miRNA signatures. Table S8. Target predictions for the dermal miRNA signatures. Table S9. Target prediction for the epidermal miRNA signature combined with deregulated transcription factors in epidermis. Table S10. Characterization of phenotype of T cell subsets. Data S1. Materials and method. Data S2. Results and discussion.
LEO Pharma A/S
Abbvie
ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
content type line 23
ISSN:0906-6705
1600-0625
1600-0625
DOI:10.1111/exd.12604