Effect of long-term corticosteroid treatment on microRNA and gene-expression profiles in COPD.
Alen FaizKatrina SteilingMirjam P RoffelDirkje S PostmaAvrum SpiraMarc E LenburgMalte BorggreweTim R EijgenraamMarnix R JonkerGerard H KoppelmannSimon D PouwelsGang LiuYuriy O AlekseyevStephen LamPieter S HiemstraPeter J SterkWim TimensCorry-Anke BrandsmaIrene H HeijinkMaarten van den BergePublished in: The European respiratory journal (2019)
The aim was to investigate whether microRNA (miRNA) expression is modulated by inhaled corticosteroid (ICS) treatmentWe performed genome-wide miRNA analysis on bronchial biopsies of 69 moderate/severe chronic obstructive pulmonary disease (COPD) patients at baseline and after 6- and 30-month treatment with the ICS fluticasone propionate or placebo. The effect of ICS on miRNA expression was validated in differentiated primary bronchial epithelial cultures, and functional studies were conducted in BEAS-2B cells. MiRNAs affected by ICS and their predicted targets were compared to an independent miRNA dataset of bronchial brushings from COPD patients and healthy controls.Treatment with ICS for both 6 and 30 months significantly altered the expression of four miRNAs, including miR-320d, which was increased during ICS treatment compared with placebo. The ICS-induced increase of miR-320d was confirmed in primary airway epithelial cells. MiR-320d negatively correlated targets were enriched for pro-inflammatory genes and were increased in the bronchial brushes of patients with lower lung function in the independent dataset. Overexpression of miR-320d in BEAS-2B cells dampened cigarette smoke extract-induced pro-inflammatory activity via inhibition of nuclear factor-κB.Collectively, we identified miR-320d as a novel mediator of ICS, regulating the pro-inflammatory response of the airway epithelium.
Keyphrases
- chronic obstructive pulmonary disease
- lung function
- cell proliferation
- long non coding rna
- gene expression
- poor prognosis
- inflammatory response
- genome wide
- long noncoding rna
- cystic fibrosis
- end stage renal disease
- dna methylation
- chronic kidney disease
- nuclear factor
- air pollution
- randomized controlled trial
- oxidative stress
- ejection fraction
- immune response
- newly diagnosed
- combination therapy
- peritoneal dialysis
- anti inflammatory
- endothelial cells
- lipopolysaccharide induced
- study protocol
- genome wide identification