Suppression of regulatory factor X 7 alleviates airway remodeling and inflammation in childhood asthma.

Abstract

Objective: Childhood asthma is a chronic heterogeneous syndrome composed of distinct disease entities or phenotypes. This study was conducted to characterize regulatory factor X 7 (RFX7) in childhood asthma.

Material and methods: Two available transcriptome datasets (GSE65204 and GSE27011) were used to analyze regulatory factor X (RFX) family members in childhood asthma. Random forest, logistic regression, and linear support vector machine (SVM) analyses were performed to construct an RFX-based classification model. Airway smooth muscle cells (ASMCs) were induced through platelet-derived growth factor-BB (PDGF-BB) for an asthma in vitro model. RFX7 expression was measured through immunoblotting. RFX7 was knocked out by transfection of RFX7 small-interfering RNAs, and then airway remodeling and inflammation were assayed.

Results: Among RFX family members, RFX3, RFX7, and RFX-associated protein displayed differential expression in childhood asthma versus healthy controls. Thus, SVM, logistic regression, and random forest-based machine learning models were built. The random forest model presented the best diagnostic efficacy (area under the curve [AUC] = 1 and 0.67 in discovery and verification sets). RFX7 was found to be effective in diagnosing childhood asthma (AUC = 0.724 and 0.775 in discovery and verification sets). In addition, RFX7 was overexpressed in PDGF-BB-stimulated ASMCs (^{✶ ✶} P < 0.01). Silencing RFX7 remarkably attenuated the proliferative and migrative capacities of ASMCs with PDGF-BB stimulation (^{✶ ✶} P < 0.01). In addition, RFX7 was positively related to neutrophil infiltration in childhood asthma, and its knockdown downregulated the levels of pro-inflammatory cytokines in PDGF-BB-stimulated ASMCs (^{✶ ✶} P < 0.01).

Conclusion: The findings of this study indicate that RFX7 is a novel molecule that is correlated with airway remodeling and inflammation in childhood asthma, providing insights into the mechanism underlying this disease and its potential clinical importance.