TY - JOUR
T1 - Effect of long-term corticosteroid treatment on microRNA and gene-expression profiles in COPD
AU - Faiz, Alen
AU - Steiling, Katrina
AU - Roffel, Mirjam P.
AU - Postma, Dirkje S.
AU - Spira, Avrum
AU - Lenburg, Marc E.
AU - Borggrewe, Malte
AU - Eijgenraam, Tim R.
AU - Jonker, Marnix R.
AU - Koppelman, Gerard H.
AU - Pouwels, Simon D.
AU - Liu, Gang
AU - Alekseyev, Yuriy O.
AU - Lam, Stephen
AU - Hiemstra, Pieter S.
AU - Sterk, Peter J.
AU - Timens, Wim
AU - Brandsma, Corry-Anke
AU - Heijink, Irene H.
AU - van den Berge, Maarten
PY - 2019
Y1 - 2019
N2 - 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.
AB - 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.
UR - https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=85065324572&origin=inward
UR - https://www.ncbi.nlm.nih.gov/pubmed/30846474
U2 - https://doi.org/10.1183/13993003.01202-2018
DO - https://doi.org/10.1183/13993003.01202-2018
M3 - Article
C2 - 30846474
SN - 0903-1936
VL - 53
JO - European respiratory journal
JF - European respiratory journal
IS - 4
ER -