Journal Article

Epithelial-Mesenchymal Transition in Asthma Airway Remodeling Is Regulated by the IL-33/CD146 Axis

Chen, Zhongqi, Hu, Fan, Wang, Zhengxia, Qian, Yan, Sun, Zhixiao, Ji, Ningfei, Huang, Mao, Wu, Chaojie, Ma, Qiyun, Zhang, Mingshun, Zhu, Ranran

2020

Overview

Epithelial-mesenchymal transition (EMT) is essential in asthma airway remodeling. IL-33 from epithelial cells is involved in pulmonary fibrosis. CD146 has been extensively explored in cancer-associated EMT. Whether IL-33 regulates CD146 in the EMT process associated with asthma airway remodeling is still largely unknown. We hypothesized that EMT in airway remodeling was regulated by the IL-33/CD146 axis. House dust mite (HDM) extract increased the expression of IL-33 and CD146 in epithelial cells. Increased expression of CD146 in HDM-treated epithelial cells could be blocked with an ST2-neutralizing antibody. Moreover, HDM-induced EMT was dependent on the CD146 and TGF-β/SMAD-3 signaling pathways. IL-33 deficiency decreased CD146 expression and alleviated asthma severity. Similarly, CD146 deficiency mitigated EMT and airway remodeling in a murine model of chronic allergic airway inflammation. Furthermore, CD146 expression was significantly elevated in asthma patients. We concluded that IL-33 from HDM extract-treated alveolar epithelial cells stimulated CD146 expression, promoting EMT in airway remodeling in chronic allergic inflammation.

• Publisher: Frontiers Media SA,Frontiers Media S.A
• Subject: Airway Remodeling / Allergens - immunology / allergy / Alveolar Epithelial Cells - metabolism / Alveoli / Animal models / Animals / Antibodies / Asthma / Asthma - etiology / Asthma - metabolism / Asthma - pathology / Biomarkers / CD146 / CD146 Antigen - genetics / CD146 Antigen - metabolism / Cell Line / Cells / Cytokines / Disease Models, Animal / Disease Susceptibility / Epithelial cells / Epithelial-Mesenchymal Transition / Female / Fibrosis / Fluorescent Antibody Technique / Hypersensitivity / IL-33 / Immunohistochemistry / Immunology / Inflammation / Interleukin-33 - genetics / Interleukin-33 - metabolism / Laboratory animals / Life sciences / Liver cancer / Lung diseases / Membranes / Metastasis / Mice / NF-kappa B - metabolism / Penicillin / Proteins / Pyroglyphidae - immunology / Respiratory Mucosa - immunology / Respiratory Mucosa - metabolism / Respiratory Mucosa - pathology / Respiratory tract diseases / Scleroderma / Signal Transduction / Smad protein / Transforming growth factor-b