Silencing of miR-10b-5p alleviates the mechanical stretch-induced proliferation of HASMCs

Abstract

MicroRNAs (miRNAs) are important mediators to human airway smooth muscle cells (HASMCs) phenotype remodeling and airway diseases. MicroRNA-10b-5p (miR-10b-5p) has been extensively studied in different fields. This study set out to probe into the effect of miR-10b-5p in cyclic mechanical stretch-induced apoptosis in HASMCs. The results showed that after 15 % deformation, 0.5 s stretching and 0.5 s cyclic mechanical stretching relaxation (0.5 Hz) occurred to HASMCs, miR-10b-5p showed up-regulation without inducing significant apoptosis. Moreover, the mRNA and protein expressions of FLT1 were reduced. Then, dual-luciferase reporter assay verified that FLT1 was targeted by miR-10b-5p, and miR-10b-5p silencing increased FLT1 expression, leading to a prolonged arrest of stretch-treated HASMCs at the G1/S stage, and increased cell apoptosis compared with control group. Furthermore, the activity of Caspase-3 was reinforced, and the ratio of Bcl-2 to Bax was markedly reduced after miR-10b-5p silencing. The current study proved that expression levels of p-PI3K and p-Akt in stretch-treated HASMCs of the inhibition group were significantly inhibited in comparison to those of the controls. The effects of miR-10b-5p overexpression are opposite to that of inhibition of miR-10b-5p in stretched HASMCs. In conclusion, this study showed that miR-10b-5p silencing could weaken the hypertrophy of HASMCs. MiR-10b-5p negatively regulated FLT1 expression, but positively regulated the PI3K/Akt pathway in HASMCs. By referring to other previous studies, we concluded that miR-10b-5p might be a potent target in the treatment of airway diseases.