期刊
PHYSIOLOGICAL RESEARCH
卷 70, 期 6, 页码 883-892出版社
ACAD SCIENCES CZECH REPUBLIC, INST PHYSIOLOGY
DOI: 10.33549/physiolres.934753
关键词
miR-18a; PDGF-BB; Airway smooth muscle cells (ASMCs); Airway remodelingv; PI3K; AKT pathway
类别
The down-regulation of miR-18a was observed in the sputum and PDGF-BB-treated ASMCs of asthma patients. PDGF-BB promoted ASMCs proliferation and migration, inhibited apoptosis, induced phenotypic transformation, and activated the PI3K/AKT pathway. MiR-18a suppressed PDGF-BB-induced ASMCs proliferation, migration, and phenotypic conversion by inhibiting the PI3K/AKT pathway, thereby attenuating airway remodeling in asthma.
The increased proliferation and migration of airway smooth muscle cells (ASMCs) is a key process in the formation of airway remodeling in asthma. In this study, we focused on the expression of mircoRNA-18a (miR-18a) in airway remodeling in bronchial asthma and its related mechanisms. ASMCs are induced by platelet-derived growth factor BB (PDGF-BB) for in vitro airway remodeling. The expression of miR-18a in sputum of asthmatic patients and healthy volunteers was detected by qRT-PCR. The expression of miR-18a was over-expressed or interfered with in PDGF-BB-treated ASMCs. Cell proliferation, apoptosis and migration were detected by MTT, flow cytometry and Transwell, respectively, the expression of contractile phenotype marker proteins (SM-22 alpha, alpha-SM-actin, calponin) and key molecules of the phosphatidylinositol 3-kinase (PI3K)/AKT pathway (PI3K, p-PI3K, AKT and p-AKT) in ASMCs were detected by Western blot. The expression of miR-18a was down-regulated in the sputum and PDGF-BB-treated ASMCs of asthma patients. PDGF-BB could promote the proliferation and migration of ASMCs and inhibit their apoptosis, it could also promote the phenotypic transformation of ASMCs and activate the PI3K/AKT pathway. MiR-18a could inhibit the proliferation, migration ability and phenotypic transformation of ASMCs induced by PDGF-BB to a certain extent and alleviate the effect of PDGF-BB in supressing apoptosis, while miR-18a could inhibit the activation of the PI3K/AKT pathway. MiR-18a inhibits PDGF-BB-induced proliferation, migration and phenotypic conversion of ASMCs by inhibiting the PI3K/AKT pathway, thus attenuating airway remodeling in asthma.
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