Dataset Information

Reticular Basement Membrane Thickness Is Associated with Growth- and Fibrosis-Promoting Airway Transcriptome Profile-Study in Asthma Patients.

ABSTRACT: Airway remodeling in asthma is characterized by reticular basement membrane (RBM) thickening, likely related to epithelial structural and functional changes. Gene expression profiling of the airway epithelium might identify genes involved in bronchial structural alterations. We analyzed bronchial wall geometry (computed tomography (CT)), RBM thickness (histology), and the bronchial epithelium transcriptome profile (gene expression array) in moderate to severe persistent (n = 21) vs. no persistent (n = 19) airflow limitation asthmatics. RBM thickness was similar in the two studied subgroups. Among the genes associated with increased RBM thickness, the most essential were those engaged in cell activation, proliferation, and growth (e.g., CDK20, TACC2, ORC5, and NEK5) and inhibiting apoptosis (e.g., higher mRNA expression of RFN34, BIRC3, NAA16, and lower of RNF13, MRPL37, CACNA1G). Additionally, RBM thickness correlated with the expression of genes encoding extracellular matrix (ECM) components (LAMA3, USH2A), involved in ECM remodeling (LTBP1), neovascularization (FGD5, HPRT1), nerve functioning (TPH1, PCDHGC4), oxidative stress adaptation (RIT1, HSP90AB1), epigenetic modifications (OLMALINC, DNMT3A), and the innate immune response (STAP1, OAS2). Cluster analysis revealed that genes linked with RBM thickness were also related to thicker bronchial walls in CT. Our study suggests that the pro-fibrotic profile in the airway epithelial cell transcriptome is associated with a thicker RBM, and thus, may contribute to asthma airway remodeling.

SUBMITTER: Bazan-Socha S

PROVIDER: S-EPMC7863966 | biostudies-literature | 2021 Jan

REPOSITORIES: biostudies-literature

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Reticular Basement Membrane Thickness Is Associated with Growth- and Fibrosis-Promoting Airway Transcriptome Profile-Study in Asthma Patients.

Bazan-Socha Stanislawa S Buregwa-Czuma Sylwia S Jakiela Bogdan B Zareba Lech L Zawlik Izabela I Myszka Aleksander A Soja Jerzy J Okon Krzysztof K Zarychta Jacek J Kozlik Paweł P Dziedzina Sylwia S Padjas Agnieszka A Wojcik Krzysztof K Kepski Michal M Bazan Jan G JG

International journal of molecular sciences 20210120 3

Airway remodeling in asthma is characterized by reticular basement membrane (RBM) thickening, likely related to epithelial structural and functional changes. Gene expression profiling of the airway epithelium might identify genes involved in bronchial structural alterations. We analyzed bronchial wall geometry (computed tomography (CT)), RBM thickness (histology), and the bronchial epithelium transcriptome profile (gene expression array) in moderate to severe persistent (<i>n</i> = 21) vs. no pe ...[more]

PMID: 33498209

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Project description:RATIONALE:There is increasing evidence that aberrant processes occurring in the airways may precede the development of idiopathic pulmonary fibrosis (IPF); however, there has been no prior confirmatory data derived from imaging studies. OBJECTIVES:To assess quantitative measures of airway wall thickness (AWT) in populations characterized for interstitial lung abnormalities (ILA) and for IPF. METHODS:Computed tomographic imaging of the chest and measures of AWT were available for 6,073, 615, 1,167, and 38 participants from COPDGene (Genetic Epidemiology of COPD study), ECLIPSE (Evaluation of COPD Longitudinally to Identify Predictive Surrogate Endpoints study), and the Framingham Heart Study (FHS) and in patients with IPF from the Brigham and Women's Hospital Herlihy Registry, respectively. To evaluate these associations, we used multivariable linear regression to compare a standardized measure of AWT (the square root of AWT for airways with an internal perimeter of 10 mm [Pi10]) and characterizations of ILA and IPF by computed tomographic imaging of the chest. RESULTS:In COPDGene, ECLIPSE, and FHS, research participants with ILA had increased measures of Pi10 compared with those without ILA. Patients with IPF had mean measures of Pi10 that were even greater than those noted in research participants with ILA. After adjustment for important covariates (e.g., age, sex, race, body mass index, smoking behavior, and chronic obstructive pulmonary disease severity when appropriate), research participants with ILA had increased measures of Pi10 compared with those without ILA (0.03 mm in COPDGene, 95% confidence interval [CI], 0.02-0.03; P < 0.001; 0.02 mm in ECLIPSE, 95% CI, 0.005-0.04; P = 0.01; 0.07 mm in FHS, 95% CI, 0.01-0.1; P = 0.01). Compared with COPDGene participants without ILA older than 60 years of age, patients with IPF were also noted to have increased measures of Pi10 (2.0 mm, 95% CI, 2.0-2.1; P < 0.001). Among research participants with ILA, increases in Pi10 were correlated with reductions in lung volumes in some but not all populations. CONCLUSIONS:These results demonstrate that measurable increases in AWT are consistently noted in research participants with ILA and in patients with IPF. These findings suggest that abnormalities of the airways may play a role in, or be correlated with, early pathogenesis of pulmonary fibrosis.

Dataset Information

Reticular Basement Membrane Thickness Is Associated with Growth- and Fibrosis-Promoting Airway Transcriptome Profile-Study in Asthma Patients.

Publications

Reticular Basement Membrane Thickness Is Associated with Growth- and Fibrosis-Promoting Airway Transcriptome Profile-Study in Asthma Patients.

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