Abstract
BackgroundmiRNAs control important cellular functions including angiogenesis/angiostasis or fibrosis and reveal altered expression during pathological processes in the lung.MethodsThe aim of the study was to investigate the expression of selected miRNAs (miR-let7f, miR-15b, miR-16, miR-20a, miR-27b, miR-128a, miR-130a, miR-192 miR-221, miR-222) in patients with pulmonary sarcoidosis (n = 94) and controls (n = 50). The expression was assessed by q-PCR in BALF cells and peripheral blood lymphocytes (PB lymphocytes). For statistical analysis, the Kruskal–Wallis test, Mann–Whitney U- test, Neuman–Keuls’ multiple comparison test, and Spearman’s rank correlation were used.ResultsIn BALF cells, significantly higher expression of miR-192 and miR-221 and lower expression of miR-15b were found in patients than controls. MiR-27b, miR-192 and miR-221 expression was significantly higher in patients without parenchymal involvement (stages I) than those at stages II-IV. Patients with acute disease demonstrated significantly higher miR-27b, miR-192 and miR-221 expression than those with insidious onset. For PB lymphocytes, patients demonstrated significantly greater miR-15b, miR-27b, miR-192, miR-221 and miR-222 expression, but lower miR-let7f and miR-130a expression, than controls. Stage I patients demonstrated significantly higher miR-16 and miR-15b expression than those in stages II-IV, and patients with the acute form demonstrated higher miR-130a and miR-15b expression. In BALF cells, miR-16 and miR-20a expression was significantly higher in patients with lung volume restriction, and miR-let7f was higher in the PB lymphocytes in patients with obturation. Several correlations were observed between the pattern of miRNA expression, lung function parameters and selected laboratory markers.ConclusionThe obtained results suggest that the studied miRNAs play a role in the pathogenesis of sarcoidosis, and that some of them might have negative prognostic value.Electronic supplementary materialThe online version of this article (doi:10.1186/s12881-016-0266-6) contains supplementary material, which is available to authorized users.
Highlights
MiRNAs control important cellular functions including angiogenesis/angiostasis or fibrosis and reveal altered expression during pathological processes in the lung
Peripheral blood (PB) lymphocytes Statistically significant differences (Mann-Whitney U- test) between patients and controls were observed for miR-15b (P = 0.00009, Mann-Whitney U- test), miR-27b (P = 0.01, Mann-Whitney U- test), miR-192 (P = 0.005, Mann-Whitney U- test), miR-221 (P, Mann-Whitney Utest), and miR-222 (P = 0.0061, Mann-Whitney U- test) with higher miRNA expression levels in sarcoidosis patients
The present study focuses on these two pathways because an important pathogenic component of sarcoidosis is pulmonary fibrosis, a condition associated with chronic inflammation, whose symptoms are known to be impaired wound healing and angiogenesis
Summary
MiRNAs control important cellular functions including angiogenesis/angiostasis or fibrosis and reveal altered expression during pathological processes in the lung. The present study evaluates the expression pattern of several miRNAs which target genes involved in proangiogenic or angiostatic functions and ECM/EMT remodeling. These are recognized as important processes in the pathogenesis of sarcoidosis, as they are involved in granulomatous formation, fibrosis, and the inhibition of the migration and proliferation of endothelial and epithelial cells [2, 4, 5, 18,19,20,21]. The analyses were performed in BALF cells and peripheral blood (PB) lymphocytes of sarcoidosis patients, using the qPCR method
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