Mechanistic analysis of Th2-type inflammatory factors in asthma

Yingjiao Qin; Chang Liu; Qi Li; Xiangdong Zhou; Jie Wang

doi:10.21037/jtd-23-1628

Mechanistic analysis of Th2-type inflammatory factors in asthma

J Thorac Dis. 2023 Dec 30;15(12):6898-6914. doi: 10.21037/jtd-23-1628. Epub 2023 Dec 26.

Authors

Yingjiao Qin^#¹, Chang Liu^#¹, Qi Li¹, Xiangdong Zhou¹, Jie Wang¹

Affiliation

¹ Department of Respiratory Diseases, The First Affiliated Hospital of Hainan Medical University, Hainan Province Clinical Medical Center of Respiratory Diseases, Haikou, China.

^# Contributed equally.

Abstract

Background: The main pathological features of asthma are widespread chronic inflammation of the airways and restricted ventilation due to airway remodeling, which involves changes in a range of regulatory pathways. While the role of T helper type 2 (Th2)-related inflammatory factors in this process is known, the detailed understanding of how genes affect protein functions during airway remodeling is still lacking. This study aims to fill this knowledge gap by integrating gene expression data and protein function analysis, providing new scientific insights for a deeper understanding of the mechanisms of airway remodeling and for further development of asthma treatment strategies.

Methods: In this study, the mechanism of Th2-related inflammatory factors in tracheal remodeling was studied through differentially expressed gene (DEG) screening, enrichment analysis, protein-protein interaction (PPI) network construction, machine learning, and the construction of a line graph model.

Results: Our study revealed that S100A14, KRT6A, S100A2, ABCA13, UBE2C, RASSF10, PSCA, PLAT, and TIMP1 may be the key genes for airway remodeling; epithelial-mesenchymal transition (EMT)-related genes GEM, TPM4, SLC6A8, and SNTB1 may be involved in airway remodeling due to asthma; IL6 may affect the occurrence of airway remodeling by binding to UBE2C protein or by regulating GEM genes, respectively; IL6 and IL9 may affect the occurrence of airway remodeling by regulating the downstream Toll-like receptor (TLR) signaling pathway and thus IL6 and IL9 may influence the occurrence of tracheal remodeling by regulating downstream TLR signaling pathways.

Conclusions: This study further mined the asthma gene microarray database through bioinformatics analysis and identified key genes and important pathways affecting airway remodeling in asthma patients, providing new ideas to uncover the mechanism of airway remodeling due to asthma and then seek new therapeutic targets.

Keywords: T helper type 2-associated inflammatory factors (Th2-associated inflammatory factors); airway inflammation; airway remodeling; asthma.