NOD-like receptor signaling and inflammasome-related pathways are highlighted in psoriatic epidermis
| Autor: | H. Annika Siitonen, Raija Sormunen, Tiina Skoog, Esko Kankuri, Kristo Nuutila, Juha Kere, Sari Suomela, Sten Linnarsson, Mari H. Tervaniemi, Shintaro Katayama, Jyrki Vuola, Outi Elomaa, Anna Johnsson |
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| Přispěvatelé: | Research Programs Unit, Department of Medical and Clinical Genetics, Research Programme for Molecular Neurology, Medicum, Clinicum, Plastiikkakirurgian yksikkö, Department of Pharmacology, Department of Dermatology, Allergology and Venereology, Esko Markus Kankuri / Principal Investigator, Juha Kere / Principal Investigator |
| Jazyk: | angličtina |
| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Keratinocytes Male Inflammasomes Nod2 Signaling Adaptor Protein Transcriptome 0302 clinical medicine Gene expression RNA-SEQ Microscopy Immunoelectron Skin Regulation of gene expression Multidisciplinary Microscopy Confocal Reverse Transcriptase Polymerase Chain Reaction Nuclear Proteins Inflammasome PYCARD ASSOCIATION Middle Aged Immunohistochemistry Cell biology medicine.anatomical_structure 030220 oncology & carcinogenesis Female medicine.drug Signal Transduction EXPRESSION GENES SUSCEPTIBILITY LOCI PROVIDES INSIGHTS NLR Proteins INNATE Biology IMMUNITY Article 03 medical and health sciences Young Adult Dermis medicine Humans Psoriasis RNA Messenger TRANSCRIPTOME Aged Gene Expression Profiling Phosphoproteins Gene expression profiling CARD Signaling Adaptor Proteins Cytoskeletal Proteins 030104 developmental biology Immunology 3111 Biomedicine Epidermis RESPONSES |
| Zdroj: | Scientific Reports |
| Popis: | Psoriatic skin differs distinctly from normal skin by its thickened epidermis. Most gene expression comparisons utilize full-thickness biopsies, with substantial amount of dermis. We assayed the transcriptomes of normal, lesional and non-lesional psoriatic epidermis, sampled as split-thickness skin grafts, with 5′-end RNA sequencing. We found that psoriatic epidermis contains more mRNA per total RNA than controls and took this into account in the bioinformatic analysis. The approach highlighted innate immunity-related pathways in psoriasis, including NOD-like receptor (NLR) signaling and inflammasome activation. We demonstrated that the NLR signaling genes NOD2, PYCARD, CARD6 and IFI16 are upregulated in psoriatic epidermis and strengthened these findings by protein expression. Interestingly, PYCARD, the key component of the inflammasome, showed an altered expression pattern in the lesional epidermis. The profiling of non-lesional skin highlighted PSORS4 and mitochondrially encoded transcripts, suggesting that their gene expression is altered already before the development of lesions. Our data suggest that all components needed for the active inflammasome are present in the keratinocytes of psoriatic skin. The characterization of inflammasome pathways provides further opportunities for therapy. Complementing previous transcriptome studies, our approach gives deeper insight into the gene regulation in psoriatic epidermis. |
| Databáze: | OpenAIRE |
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