Effect of long-term corticosteroid treatment on microRNA and gene-expression profiles in COPD

Alen Faiz; Katrina Steiling; Mirjam P. Roffel; Dirkje S. Postma; Avrum Spira; Marc E. Lenburg; Malte Borggrewe; Tim R. Eijgenraam; Marnix R. Jonker; Gerard H. Koppelman; Simon D. Pouwels; Gang Liu; Yuriy O. Alekseyev; Stephen Lam; Pieter S. Hiemstra; Peter J. Sterk; Wim Timens; Corry-Anke Brandsma; Irene H. Heijink; Maarten van den Berge

doi:10.1183/13993003.01202-2018

Effect of long-term corticosteroid treatment on microRNA and gene-expression profiles in COPD

Alen Faiz^*, Katrina Steiling, Mirjam P. Roffel, Dirkje S. Postma, Avrum Spira, Marc E. Lenburg, Malte Borggrewe, Tim R. Eijgenraam, Marnix R. Jonker, Gerard H. Koppelman, Simon D. Pouwels, Gang Liu, Yuriy O. Alekseyev, Stephen Lam, Pieter S. Hiemstra, Peter J. Sterk, Wim Timens, Corry-Anke Brandsma, Irene H. Heijink, Maarten van den Berge

^*Corresponding author voor dit werk

Groningen Research Institute for Asthma and COPD

Onderzoeksoutput: Article › Academic › peer review

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The aim was 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 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-kappa B.

Collectively, we identified miR-320d as a novel mediator of ICS, regulating the pro-inflammatory response of the airway epithelium.

Originele taal-2	English
Artikelnummer	1801202
Aantal pagina's	12
Tijdschrift	European Respiratory Journal
Volume	53
Nummer van het tijdschrift	4
Vroegere onlinedatum	2019
DOI's	https://doi.org/10.1183/13993003.01202-2018
Status	Published - 1-apr.-2019

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Faiz, A., Steiling, K., Roffel, M. P., Postma, D. S., Spira, A., Lenburg, M. E., Borggrewe, M., Eijgenraam, T. R., Jonker, M. R., Koppelman, G. H., Pouwels, S. D., Liu, G., Alekseyev, Y. O., Lam, S., Hiemstra, P. S., Sterk, P. J., Timens, W., Brandsma, C.-A., Heijink, I. H., & van den Berge, M. (2019). Effect of long-term corticosteroid treatment on microRNA and gene-expression profiles in COPD. European Respiratory Journal, 53(4), Artikel 1801202. https://doi.org/10.1183/13993003.01202-2018

@article{86798b9c7a0f4ed38d2fe0f98be55036,

title = "Effect of long-term corticosteroid treatment on microRNA and gene-expression profiles in COPD",

abstract = "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-kappa B.Collectively, we identified miR-320d as a novel mediator of ICS, regulating the pro-inflammatory response of the airway epithelium.",

keywords = "OBSTRUCTIVE PULMONARY-DISEASE, BRONCHIAL EPITHELIAL-CELLS, INDUCED DAMP RELEASE, CIGARETTE-SMOKE, LUNG-FUNCTION, INFLAMMATION, SUSCEPTIBILITY, FLUTICASONE",

author = "Alen Faiz and Katrina Steiling and Roffel, {Mirjam P.} and Postma, {Dirkje S.} and Avrum Spira and Lenburg, {Marc E.} and Malte Borggrewe and Eijgenraam, {Tim R.} and Jonker, {Marnix R.} and Koppelman, {Gerard H.} and Pouwels, {Simon D.} and Gang Liu and Alekseyev, {Yuriy O.} and Stephen Lam and Hiemstra, {Pieter S.} and Sterk, {Peter J.} and Wim Timens and Corry-Anke Brandsma and Heijink, {Irene H.} and {van den Berge}, Maarten",

note = "Copyright {\textcopyright}ERS 2019.",

year = "2019",

month = apr,

day = "1",

doi = "10.1183/13993003.01202-2018",

language = "English",

volume = "53",

journal = "European Respiratory Journal",

issn = "0903-1936",

publisher = "EUROPEAN RESPIRATORY SOC JOURNALS LTD",

number = "4",

}

Faiz, A, Steiling, K, Roffel, MP, Postma, DS, Spira, A, Lenburg, ME, Borggrewe, M, Eijgenraam, TR , Jonker, MR , Koppelman, GH , Pouwels, SD, Liu, G, Alekseyev, YO, Lam, S, Hiemstra, PS, Sterk, PJ, Timens, W , Brandsma, C-A , Heijink, IH & van den Berge, M 2019, 'Effect of long-term corticosteroid treatment on microRNA and gene-expression profiles in COPD', European Respiratory Journal, vol. 53, nr. 4, 1801202. https://doi.org/10.1183/13993003.01202-2018

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 - 2019/4/1

Y1 - 2019/4/1

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-kappa B.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-kappa B.Collectively, we identified miR-320d as a novel mediator of ICS, regulating the pro-inflammatory response of the airway epithelium.

KW - OBSTRUCTIVE PULMONARY-DISEASE

KW - BRONCHIAL EPITHELIAL-CELLS

KW - INDUCED DAMP RELEASE

KW - CIGARETTE-SMOKE

KW - LUNG-FUNCTION

KW - INFLAMMATION

KW - SUSCEPTIBILITY

KW - FLUTICASONE

U2 - 10.1183/13993003.01202-2018

DO - 10.1183/13993003.01202-2018

M3 - Article

C2 - 30846474

SN - 0903-1936

VL - 53

JO - European Respiratory Journal

JF - European Respiratory Journal

IS - 4

M1 - 1801202

ER -

Effect of long-term corticosteroid treatment on microRNA and gene-expression profiles in COPD

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