Airway Epithelial MiRNA Expression is Altered in Asthma

Overview

Journal Am J Respir Crit Care Med

Specialty Critical Care

Date 2012 Sep 8

PMID 22955319

Citations 136

Authors

Owen D Solberg

Edwin J Ostrin

Michael I Love

Jeffrey C Peng

Nirav R Bhakta

Lydia Hou

Christine Nguyen

Margaret Solon

Cindy Nguyen

Andrea J Barczak

Lorna T Zlock

Denitza P Blagev

Walter E Finkbeiner

K Mark Ansel

Joseph R Arron

David J Erle

Prescott G Woodruff

Affiliations

Soon will be listed here.

Abstract

Rationale: Changes in airway epithelial cell differentiation, driven in part by IL-13, are important in asthma. Micro-RNAs (miRNAs) regulate cell differentiation in many systems and could contribute to epithelial abnormalities in asthma.

Objectives: To determine whether airway epithelial miRNA expression is altered in asthma and identify IL-13-regulated miRNAs.

Methods: We used miRNA microarrays to analyze bronchial epithelial brushings from 16 steroid-naive subjects with asthma before and after inhaled corticosteroids, 19 steroid-using subjects with asthma, and 12 healthy control subjects, and the effects of IL-13 and corticosteroids on cultured bronchial epithelial cells. We used quantitative polymerase chain reaction to confirm selected microarray results.

Measurements And Main Results: Most (12 of 16) steroid-naive subjects with asthma had a markedly abnormal pattern of bronchial epithelial miRNA expression by microarray analysis. Compared with control subjects, 217 miRNAs were differentially expressed in steroid-naive subjects with asthma and 200 in steroid-using subjects with asthma (false discovery rate < 0.05). Treatment with inhaled corticosteroids had modest effects on miRNA expression in steroid-naive asthma, inducing a statistically significant (false discovery rate < 0.05) change for only nine miRNAs. qPCR analysis confirmed differential expression of 22 miRNAs that were highly differentially expressed by microarrays. IL-13 stimulation recapitulated changes in many differentially expressed miRNAs, including four members of the miR-34/449 family, and these changes in miR-34/449 family members were resistant to corticosteroids.

Conclusions: Dramatic alterations of airway epithelial cell miRNA levels are a common feature of asthma. These alterations are only modestly corrected by inhaled corticosteroids. IL-13 effects may account for some of these alterations, including repression of miR-34/449 family members that have established roles in airway epithelial cell differentiation. Clinical trial registered with www.clinicaltrials.gov (NCT 00595153).

Citing Articles

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Kierbiedz-Guzik N, Sozanska B Int J Mol Sci. 2025; 26(1.

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MicroRNA Profiling of the Inflammatory Response after Early and Late Asthmatic Reaction.

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The RNA binding proteins and are dysregulated in airway epithelium in human and a murine model of asthma.

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miR-223: a key regulator of pulmonary inflammation.

Shi M, Lu Q, Zhao Y, Ding Z, Yu S, Li J Front Med (Lausanne). 2023; 10:1187557.

PMID: 37465640 PMC: 10350674. DOI: 10.3389/fmed.2023.1187557.

Nasal airway microRNA profiling of infants with severe bronchiolitis and risk of childhood asthma: a multicentre prospective study.

Zhu Z, Freishtat R, Harmon B, Hahn A, Teach S, Perez-Losada M Eur Respir J. 2023; 62(2).

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