MicroRNA-30a Targets ATG5 and Attenuates Airway Fibrosis in Asthma by Suppressing Autophagy

• Published in: Inflammation 2020-02, Vol.43 (1), p.44-53
• Main Authors: Li, Bin Bin, Chen, Yun long, Pang, Fuzhen
• Format: Article
• Language: English
• Subjects: Adolescent; Airway Remodeling; Animal models; Animals; Asthma; Asthma - genetics; Asthma - metabolism; Asthma - pathology; Asthma - physiopathology; Autophagy; Autophagy-Related Protein 5 - genetics; Autophagy-Related Protein 5 - metabolism; Biomedical and Life Sciences; Biomedicine; Case-Control Studies; Cell Line; Child; Children; Disease Models, Animal; Epithelial cells; Epithelial Cells - metabolism; Epithelial Cells - pathology; Female; Fibrosis; Humans; Immunology; Inflammation; Internal Medicine; Lung - metabolism; Lung - pathology; Lung - physiopathology; Male; Mice, Inbred C57BL; MicroRNAs; MicroRNAs - genetics; MicroRNAs - metabolism; miRNA; Original Article; Ovalbumin; Pathology; Phagocytosis; Pharmacology/Toxicology; Respiratory tract; Respiratory tract diseases; Rheumatology; Signal Transduction
• ISSN: 0360-3997; 1573-2576
• DOI: 10.1007/s10753-019-01076-0

Asthma is the most common chronic disease of childhood, chronic airway inflammation; bronchial tissue fibrosis, is a pathological feature common to children asthma, and an emerging data has indicted that autophagy plays critical roles in airway inflammation and fibrosis-mediated airway remodeling. The aim of this study was to examine whether the antifibrotic effect of epithelial microRNAs (miRNAs) relies on regulating autophagy-mediated airway remodeling and to identify the factors involved and the underlying mechanisms. Our results showed miR-30a were downregulated in children with asthma and ovalbumin (OVA) mouse model in parallel with the upregulation of autophagy-related proteins; moreover, we observed miR-30a inhibited the autophagy by downregulated autophagy-related 5 (ATG5). Then, we observed that overexpression of miR-30a suppressed the fibrogenesis and autophagic flux which was stimulated by interleukin-33 (IL-33) in bronchial epithelial cells. In vivo experiments showed that miR-30a overexpression decreased airway remodeling by decreased autophagy. This study uncovered a previously unrecognized antifibrotic role of miR-30a in asthma, in IL-33-induced lung epithelial cells in vitro , and in a murine model of OVA-induced airway inflammation in vivo and explored the underlying mechanisms.