MiR-18a Inhibits PI3K/AKT Signaling Pathway to Regulate PDGF-BB-Induced Airway Smooth Muscle Cell Proliferation and Phenotypic Transformation

Abstract

The increased proliferation and migration of airway smooth muscle cells (ASMCs) is a key process in the formation of airwayremodeling in asthma. In this study, we focused on theexpression of mircoRNA-18a (miR-18a) in airway remodeling inbronchial asthma and its related mechanisms. ASMCs are inducedby platelet-derived growth factor BB (PDGF-BB) for in vitroairway remodeling. The expression of miR-18a in sputum ofasthmatic patients and healthy volunteers was detected byqRT-PCR. The expression of miR-18a was over-expressed orinterfered with in PDGF-BB-treated ASMCs. Cell proliferation,apoptosis and migration were detected by MTT, flow cytometryand Transwell, respectively, the expression of contractilephenotype marker proteins (SM-22α, α-SM-actin, calponin) andkey molecules of the phosphatidylinositol 3-kinase (PI3K)/AKTpathway (PI3K, p-PI3K, AKT and p-AKT) in ASMCs were detectedby Western blot. The expression of miR-18a was down-regulatedin the sputum and PDGF-BB-treated ASMCs of asthma patients.PDGF-BB could promote the proliferation and migration of ASMCsand inhibit their apoptosis, it could also promote the phenotypictransformation of ASMCs and activate the PI3K/AKT pathway.MiR-18a could inhibit the proliferation, migration ability andphenotypic transformation of ASMCs induced by PDGF-BB to a certain extent and alleviate the effect of PDGF-BB in supressingapoptosis, while miR-18a could inhibit the activation of thePI3K/AKT pathway. MiR-18a inhibits PDGF-BB-inducedproliferation, migration and phenotypic conversion of ASMCs byinhibiting the PI3K/AKT pathway, thus attenuating airwayremodeling in asthma