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… Click to show full abstract
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.
               
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