| Autor: |
Duecker, Ruth Pia, de Mir Messa, Inés, Jerkic, Silvija-Pera, Kochems, Annalena, Gottwald, Gabriele, Moreno Galdó, Antonio |
| Přispěvatelé: |
Institut Català de la Salut, [Duecker RP, Jerkic SP, Kochems A, Gottwald G] Division for Allergy, Pneumology and Cystic Fibrosis, Department for Children and Adolescence, Goethe University, Frankfurt, Germany. [De Mir Messa I] Unitat de Pneumologia Pediàtrica i Fibrosi Quística, Servei de Pediatria, Vall d’Hebron Hospital Universitari, Barcelona, Spain. Universitat Autònoma de Barcelona, Bellaterra, Spain. [Moreno-Galdó A] Unitat de Pneumologia Pediàtrica i Fibrosi Quística, Servei de Pediatria, Vall d’Hebron Hospital Universitari, Barcelona, Spain. Universitat Autònoma de Barcelona, Bellaterra, Spain. CIBER of Rare Diseases (CIBERER), Instituto de Salud Carlos III (ISCIII), Madrid, Spain, Vall d'Hebron Barcelona Hospital Campus |
| Jazyk: |
angličtina |
| Rok vydání: |
2022 |
| Předmět: |
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| Zdroj: |
Scientia |
| Popis: |
Inflammation; MicroRNA; Post‐infectious bronchiolitis obliterans Inflamación; MicroARN; Bronquiolitis obliterante posinfecciosa Inflamació; MicroARN; Bronquiolitis obliterant postinfecciosa Objectives Post-infectious bronchiolitis obliterans (PiBO) is a rare, chronic disease initiated by severe infection and followed by perpetuating inflammation and obliteration of the small airways. MicroRNAs (miRNAs) have been proposed to play a central role as epigenetic regulators, which control resolution and prevent the uncontrolled progress of inflammation. The aim of this study was to define biomarkers on the level of post-transcriptional gene regulation in order to characterise PiBO. Methods A total of 39 patients with well-defined PiBO and 31 controls from two centres, Barcelona, Spain, and Frankfurt, Germany, were analysed by next-generation sequencing (NGS). The evaluation of the biological targets of the miRNAs was performed by pathway enrichment analysis and protein–protein interaction network analysis respectively. Results Patients with PiBO had significantly lower lung function values and increased airway inflammation in induced sputum as indicated by total cell counts, neutrophils, IL-1β, IL-6, IL-8 and TGF-β compared to controls. Next-generation sequencing analysis revealed a total of 22 dysregulated miRNAs, which passed significance threshold for Padj ≤ 0.001 with 17 being upregulated and 5 being downregulated. Of these dysregulated miRNAs, miR-335-5p, miR-186-5p, miR-30b-5p and miR-30c-5p were further validated using qRT-PCR. Interestingly, these miRNAs are functionally implicated in cytokine–cytokine receptor interaction, TGF-β signalling and FoxO signalling pathway and significantly correlated with lung function values (FEV1). Conclusion Our results demonstrate an aberrant miRNA expression profile in PiBO, which impacts pathways responsible for the regulation of inflammation and fibrosis. The defined miRNAs are useful biomarkers and should be assessed as potential target in the field of miRNA therapeutics. Starke Lunge Foundation. Grant Number: I 1325d 04/11(6)-78 |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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