A comprehensive gene expression profile of allergic rhinitis-derived nasal fibroblasts and the potential mechanism for its phenotype

Abstract

Background Allergic rhinitis (AR) is a common immunoglobulin E-mediated immune response involved various cell types, while the role of nasal fibroblasts (NFs) in the pathogenesis of AR is less understood. Purpose The study aimed to uncover the gene expression profile of AR-derived NFs and the potential mechanism for the changed phenotype of AR-NFs. Research Design The primary NFs were isolated from 3 AR patients (AR-NFs) and 3 controls (Ctrl-NFs), and the proliferation, migration and interleukins production abilities of NFs were detected respectively. RNA-sequence was used to identify differentially expressed genes (DEGs) in AR-NFs. Transcription factor (TF) regulatory network and bioinformatic analyses were both conducted to clarify the biological roles of DEGs including the TFs. The DEG with the highest validated |fold change (FC)| value, detected by qPCR, was selected for further confirmation. Results AR-NFs showed a higher proliferation and migration abilities as well as released higher levels of IL-33 and IL-6, compared to Ctrl-NFs. A total of 729 DEGs were screened out in AR-NFs. TF regulatory network indicated that BARX homeobox 1 (BARX1) and forkhead box L1 were the major node TFs. Bioinformatic analyses showed that a large number of DEGs including several target genes of BARX1 were both enriched cytokine-related GO terms, and immune- or inflammation-related pathways. BARX1 had the highest |FC| value, and silencing BARX1 in AR-NFs resulted in the significant downregulation of proliferation and migration abilities, and the production of interleukins. Conclusions Our study for the first time provided the gene expression profile of AR-derived NFs, and BARX1 could be developed as a potent target to alleviate the pathogenesis of AR.

ZFP36 loss-mediated BARX1 stabilization promotes malignant phenotypes by transactivating master oncogenes in NSCLC

“…We identified BARX1 as a key regulator involved in NSCLC progression by combining the ESTIMATE score with the transcriptome-based differently expressed genes analysis, and here mainly focused on its oncogenic role and regulation. Although a recent study showed that silencing BARX1 resulted in downregulated production of interleukins in allergic rhinitis-derived nasal fibroblasts, the exact role of BARX1 in tumor immune response remains to be elucidated [ 33 ].…”

Gene Signatures and Associated Transcription Factors of Allergic Rhinitis: KLF4 Expression Is Associated with Immune Response

“…Several studies have been conducted to identify candidate genes associated with rhinitis. However, these studies were conducted with limited sample numbers and require further evaluation [ 9 , 26 ]. As such, the molecular mechanisms underlying AR remain unclear.…”

Effect of MP‐AzeFlu compared to monotherapy on COX‐2, PGE2, and EP2 gene expression in upper airway mucosa

“…For example, primary nasal fibroblasts isolated from patients with AR showed higher proliferation and migration abilities and increased expression of interleukin (IL)‐33 and IL‐6 compared to controls. 6 Furthermore, it has been demonstrated that human fibroblasts from patients with AR release thymic stromal lymphopoietin (TSLP) in response to IL‐17A. Since IL‐17A has been implicated in the pathogenesis of AR and TSLP modifies the immune response toward a Th2 phenotype, these results suggest that fibroblasts play a role in the development of AR.…”

“…Several studies have demonstrated that fibroblasts release proinflammatory mediators involved in the molecular mechanisms present in the airways of patients suffering from AR. For example, primary nasal fibroblasts isolated from patients with AR showed higher proliferation and migration abilities and increased expression of interleukin (IL)‐33 and IL‐6 compared to controls 6 . Furthermore, it has been demonstrated that human fibroblasts from patients with AR release thymic stromal lymphopoietin (TSLP) in response to IL‐17A.…”