RT Journal Article
SR Electronic
T1 Effect of long-term corticosteroid treatment on microRNA and gene-expression profiles in Chronic Obstructive Pulmonary Disease
JF European Respiratory Journal
JO Eur Respir J
FD European Respiratory Society
SP 1801202
DO 10.1183/13993003.01202-2018
A1 Alen Faiz
A1 Katrina Steiling
A1 Mirjam P. Roffel
A1 Dirkje S. Postma
A1 Avrum Spira
A1 Marc E. Lenburg
A1 Malte Borggrewe
A1 Tim R. Eijgenraam
A1 Marnix R. Jonker
A1 Gerard H. Koppelman
A1 Simon D. Pouwels
A1 Gang Liu
A1 Yuriy O. Alekseyev
A1 Stephen Lam
A1 Pieter S. Hiemstra
A1 Peter J. Sterk
A1 Wim Timens
A1 Corry-Anke Brandsma
A1 Irene H. Heijink
A1 Maarten van den Berge
YR 2019
UL http://erj.ersjournals.com/content/early/2019/01/30/13993003.01202-2018.abstract
AB To investigate whether microRNA (miRNA) expression is modulated by inhaled corticosteroid (ICS) treatment, we performed genome-wide miRNA analysis on bronchial biopsies of 69 moderate/severe COPD patients at baseline and after 6- and 30-month treatment with the ICS fluticasone propionate (FP) 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 4 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 (NF)-κB. Collectively, we identified miR-320d as a novel mediator of ICS, regulating the pro-inflammatory response of the airway epithelium.FootnotesThis manuscript has recently been accepted for publication in the European Respiratory Journal. It is published here in its accepted form prior to copyediting and typesetting by our production team. After these production processes are complete and the authors have approved the resulting proofs, the article will move to the latest issue of the ERJ online. Please open or download the PDF to view this article.Conflict of interest: Alen FaizConflict of interest: Dr. Steiling has a patent “Biomarkers of COPD disease activity” pending.Conflict of interest: P. RoffelConflict of interest: S. PostmaConflict of interest: Avrum SpiraConflict of interest: E. LenburgConflict of interest: Malte BorggreweConflict of interest: R. EijgenraamConflict of interest: R. JonkerConflict of interest: H. KoppelmanConflict of interest: D. PouwelsConflict of interest: Gang LiuConflict of interest: Dr. Alekseyev has nothing to disclose.Conflict of interest: Stephen LamConflict of interest: S. HiemstraConflict of interest: Dr. Sterk reports grants from GlaxoSmithKline, grants from Dutch Government, during the conduct of the study.Conflict of interest: Wim TimensConflict of interest: Corry-Anke BrandsmaConflict of interest: H. HeijinkConflict of interest: Maarten van den Berge