MiRNA-192-5p attenuates airway remodeling and autophagy in asthma by targeting MMP-16 and ATG7

Abstract

Asthma is a chronic lung inflammatory disease with high incidence. MicroRNA-192-5p (miR-192-5p) was down-regulated in asthmatics. However, the role of miR-192-5p in asthma is still unclear. In current study, in vitro, the overexpression of miR-192-5p, matrix metalloproteinase (MMP)-16 and autophagy related 7 (ATG7) was conducted in airway smooth muscle cells (ASMCs). We found that miR-192-5p suppressed cell proliferation, and decreased MMP-16 and ATG7 expression. MMP-16 and ATG7 promoted cell proliferation, and further alleviated the down-regulation of miR-192-5p on proliferation of ASMCs. in vivo, miR-192-5p was down-regulated in asthma mice, and involved in improvement of asthma mice. MiR-192-5p was demonstrated to alleviate inflammation in asthma mice, including decreasing the level of ovalbumin (OVA)-specific IgE, interleukin (IL)-4, IL-5, IL-13, iNOS and COX-2. Moreover, the attenuation of airway remodeling induced by miR-192-5p in asthma mice were expressed by the reduction of fibroblast growth factor-23 (FGF-23) level, decrease in concentrations of MMP-2 and MMP-9 as well as down-regulation of collagen I deposition. Further, miR-192-5p also caused the suppression of autophagy in asthma mice, exhibiting a decrease in LC3II/I, beclin-1 and ATG7, and an increase in p62. Importantly, MMP-16 and ATG7 were confirmed to be targets of miR-192-5p. Therefore, our results indicate that miRNA-192-5p may attenuate airway remodeling and autophagy in asthma via targeting MMP-16 and ATG7.

Keywords: Asthma; Autophagy; Remodeling; miR-192-5p.