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.

Interactions via α2β1 Cell Integrin May Protect against the Progression of Airway Structural Changes in Asthma

“…Asthma patients with persistent airflow limitation were characterized by altered airway geometry, mainly increased WTR and WAR in the right bronchi, compared to patients without persistent airflow limitation, which stays in line with previously published reports [12,13,27]. In contrast, well-defined signs of remodeling in bronchial mucosae, such as RBM thickness and collagen deposits [11], were comparable in both studied subgroups.…”

“…Various features of airway remodeling, such as loss of epithelial cells and mucus cell hyperplasia, RBM thickening, and smooth muscle hypertrophy, can be described using a histological examination of airway mucosa [11]. However, emerging non-invasive methods, including lung computed tomography (CT) imaging, provide important remodeling measures that might be useful in quantifying bronchial wall thickening in a standardized and more comprehensive way [12,13].…”

RNF13 Dileucine Motif Variants L311S and L312P Interfere with Endosomal Localization and AP-3 Complex Association

“…RNF13 plays a role in myogenesis, tumorigenesis, and cell proliferation [29,32,33]. Recent studies have shown that RNF13 expression in atherosclerosis plaques is upregulated [34], while it is downregulated in uveal melanoma [35] and asthma [36]. Ectopic expression of RNF13 inhibits myoblast proliferation, whereas treatment with myostatin, a muscle growth inhibitor, upregulates RNF13 expression [32].…”

From Drosophila to Human: Biological Function of E3 Ligase Godzilla and Its Role in Disease

“…RNF13 altered expression is not only linked to cancer. In fact, recent studies have shown that RNF13 gene expression is upregulated in atherosclerotic plaques [70] and downregulated in asthma [71]. Also, Huang et al discovered that the microRNA miR-32-3p regulates the expression of RNF13 [72].…”