miR-20a-5p ameliorates ovalbumin (OVA)-induced mouse model of allergic asthma through targeting ATG7-regulated cell death, fibrosis and inflammation

摘要

Autophagy plays an essential role in modulating asthma progression. MiR-20a-5p can regulate autophagy, but its effects on allergic asthma are still unclear. The aim of this study was to explore the potential of miR-20a-5p on autophagy-modulated airway remodeling and to reveal the underlying molecular mechanisms. We found that miR-20a-5p expression was markedly down-regulated in lung of ovalbumin (OVA)-induced mouse model with allergic asthma and in cells stimulated by OVA. Meanwhile, autophagy, apoptosis, fibrosis and inflammatory response were detected in pulmonary tissues from OVA-treated mice. Importantly, luciferase assays showed that ATG7 was a target of miR-20a-5p. We also found that miR-20a-5p over-expression markedly reduced ATG7, while its inhibition promoted ATG7 in cells. In addition, over-expressing miR-20a-5p in OVA-treated cells significantly decreased ATG7 expression levels, along with markedly reduced autophagy, apoptotic cell death, fibrosis and inflammatory response. These results were similar to the effects of autophagy inhibitor 3-Methyladenine (3-MA), indicating that miR-20a-5p was involved in autophagy-induced apoptosis, fibrosis and inflammation. In vivo experiments further demonstrated that miR-20a-5p over-expression was associated with ATG7 reduction in parallel with the alleviated airway remodeling in OVA-treated mice also through suppressing collagen accumulation, apoptosis and inflammation. Similarly, animal studies further confirmed that miR-20a-5p functioned as an autophagy inhibitor to mitigate allergic asthma development. Therefore, miR-20a-5p may be a promising biomarker and therapeutic target during asthma progression by regulating ATG7-modulated autophagy.