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

Abstract

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. Thestudy aimed to uncover the gene expression profile of AR-derived NFs and the potential mechanism for the changed phenotype of AR-NFs. The primary NFs were isolated from 3 AR patients (AR-NFs) and 3 controls (Ctrl-NFs), andtheproliferation, migration and interleukinsproduction abilities of NFs were detected respectively. RNA-sequence was usedto identify differentially expressed genes (DEGs) in AR-NFs. Transcription factor (TF) regulatory networkand bioinformatic analyseswere 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. 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. 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.