Artikel
Disease-associated micro-RNAs in respiratory tissue and sera from Granulomatosis with Polyangiitis (GPA)
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Veröffentlicht: | 12. September 2014 |
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Gliederung
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Einleitung: Dysregulated miRNAs have a pathogenic impact and a potential as prognostic biomarkers in autoimmune diseases such as RA, Sjögren’s or inflammatory bowel diseases. Here we investigated miRNA tissue signatures in GPA and related them to their potential role in GPA pathogenesis.
Methoden: 847 miRNAs were screened (Affymetrix® microarray) for a tissue specific signature (20 GPA, 10 healthy controls/HC, 10 chronic rhinosinusitis/CRS). In an independent validation cohort (tissue and sera from 14 GPA-patients, 10 disease controls: CRS and Crohn’s/CD) 12 miRNAs were examined by qPCR. Validated and computational miRNA targets were identified by mirDIP algorithms (http://ophid.utoronto.ca/mirDIP/).
Ergebnisse: qPCR confirmed alteration of 6 out of 24 microarray-screened miRNAs in GPA sera. Differential tissue expression of miR-10b, -99a/100, -125b, -532-3p compared to Crohn’s may reflect a GPA-specific process. qPCR did not establish differences between GPA and CRS tissue. Predicted targets of GPA-associated miRNAs are proteinase-3 and LAMP-2 (ANCA autoantigen in GPA). Validated targets include MICB (NKD2 ligand), BLIMP-1, IRF4 (B-cell differentiation), matrix metalloproteinases, NFAT1 (TH1 response) and lactoferrin (another ANCA autoantigen).
Schlussfolgerung: qPCR confirmed GPA-associated miRNA dysregulation in tissue and serum. Distinctive miRNA profiles in GPA, CRS and CD suggest disparate pathophysiological mechanisms. In GPA dysregulated miRNAs might contribute to GPA pathogenesis by modifying expression of ANCA autoantigens, B-cell differentiation factors, Th1 response and tissue degradation. Considering the diagnostic, prognostic and therapeutic applications of miRNAs in other diseases, validating and relating predicted targets to clinical aspects of GPA will help to understand this disease on a molecular level.