MicroRNA-30a Targets ATG5 and Attenuates Airway Fibrosis in Asthma by Suppressing Autophagy
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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.
KEY WORDSmiR-30a ATG5 Autophagy Airway fibrosis Asthma
Compliance with Ethical Standards
All mouse experiments were approved by research committee of Zhejiang University. This study was approved by the Hangzhou Children’s Hospital and written informed consent was obtained from all patients.
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