Glucocorticoid-induced Changes in Gene Expression of Airway Smooth Muscle in Patients with Asthma

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art_MAUAD_Glucocorticoid_induced_Changes_in_Gene_Expression_of_Airway_2013.PDF (1 MB)
Citações na Scopus
56
Tipo de produção
article
Data de publicação
2013
DOI
Scopus
Web of Science
PubMed
Título da Revista
ISSN da Revista
Título do Volume
Editora
AMER THORACIC SOC
Autores
YICK, Ching Yong
ZWINDERMAN, Aeilko H.
KUNST, Peter W.
GRUNBERG, Katrien
FLUITER, Kees
BEL, Elisabeth H.
LUTTER, Rene
BAAS, Frank
STERK, Peter J.
Citação
AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE, v.187, n.10, p.1076-1084, 2013
Projetos de Pesquisa
Unidades Organizacionais
Fascículo
Resumo
Rationale: Glucocorticoids are the mainstay of asthma therapy. However, it is unclear whether the benefits of glucocorticoids in asthma are merely based on antiinflammatory properties. Glucocorticoids may also alter gene expression of airway smooth muscle (ASM). We hypothesized that the gene expression profile of the ASM layer in endobronchial biopsies of patients with asthma is altered by oral glucocorticoid therapy as compared with placebo. Objectives: First, we investigated the change in ASM transcriptomic profile in endobronchial biopsies after 14 days of oral glucocorticoid therapy. Second, we investigated the association between changes in ASM transcriptomic profile and lung function. Methods: Twelve steroid-free patients with atopic asthma were included in this double-blind intervention study. Endobronchial biopsies were taken before and after 14 days of oral prednisolone (n = 6) or placebo (n = 6). RNA of laser-dissected ASM was sequenced (RNA-Seq) using GS FLX+(454/Roche). Gene networks were identified by Ingenuity Pathway Analysis. RNA-Seq reads were assumed to follow a negative binomial distribution. At the current sample size the estimated false discovery rate was approximately 3%. Measurements and Main Results: Fifteen genes were significantly changed by 14 days of oral prednisolone. Two of these genes (FAM129A, SYNPO2) were associated with airway hyperresponsiveness (provocative concentration of methacholine causing a 20% drop in FEV1: r = -0.740, P < 0.01; r = -0.746, P < 0.01). Pathway analysis revealed three gene networks that were associated with cellular functions including cellular growth, proliferation, and development. Conclusions: Oral prednisolone changes the transcriptomic profile of the ASM layer in asthma. This indicates that in parallel to antiinflammatory properties, glucocorticoids also exert effects on gene expression of ASM, which is correlated with improved airway function.
Palavras-chave
asthma, airway smooth muscle, RNA-Seq, glucocorticoids, prednisolone
URI
https://observatorio.fm.usp.br/handle/OPI/2163
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Coleções
Artigos e Materiais de Revistas Científicas - FM/MPT
Artigos e Materiais de Revistas Científicas - HC/ICHC
Artigos e Materiais de Revistas Científicas - LIM/05
Artigos e Materiais de Revistas Científicas - ODS/03