期刊
JOURNAL OF ASTHMA AND ALLERGY
卷 14, 期 -, 页码 71-80出版社
DOVE MEDICAL PRESS LTD
DOI: 10.2147/JAA.S291333
关键词
lncRNA H19; asthmatic children; airway smooth muscle cell; miR-21; airway remodeling
In this study, down-regulation of LncRNA H19 and up-regulation of microRNA-21 were observed in serum samples of children with asthma and PDGF-BB-stimulated ASMCs. Overexpression of H19 inhibited proliferation and migration of ASMCs induced by PDGF-BB, and this effect was mediated through the miR-21/PTEN/Akt axis. H19 promoted PTEN expression by sponging miR-21 and suppressed Akt phosphorylation.
Background: LncRNA H19 expression is down-regulated in patients with asthma. The hyperplasia of airway smooth muscle cells (ASMCs) promotes the development of airway remodeling in asthma. Therefore, we attempted to evaluate the regulatory function of H19 in the proliferation and migration of ASMCs. Methods: The expressions of H19 and miR-21 were detected using qRT-PCR. PDGF-BB-induced abnormal proliferation and migration of ASMCs was used as the airway remodeling model in vitro. The expressions of H19 and miR-21 were modified by transfection with pcDNA3.1-H19 and miR-21 mimic, respectively. CCK-8 assay, flow cytometry-based cell cycle analysis was conducted to examine the proliferation ability of ASMCs. The migration ability was measured by transwell assay. Dual-luciferase reporter system was carried out to find the potential relationship between miR-21 and H19 or PTEN. Western blot was conducted to detect the expressions of PCNA, MMP-9, alpha-SMA, PTEN, and the phosphorylation level of Akt. Results: LncRNA-H19 expression was decreased and microRNA-21 expression was increased in serum samples of children with asthma and PDGF-BB-stimulated ASMCs. Overexpression of H19 reduced the proliferation and migration ability of ASMCs with PDGF-BB treatment and these changes were reversed by miR-21 mimic. H19 promoted the protein level of PTEN via sponging miR-21. Overexpression of H19 suppressed miR-21-induced phosphorylation of Akt, and the suppression effect of H19 on phosphorylation of Akt was significantly reduced after transfecting shPTEN in ASMCs. Conclusion: In this study, overexpression of H19 suppressed the proliferation and migration of ASMCs induced by PDGF-BB via miR-21/PTEN/Akt axis, which could be a potential biomarker and target for treating hyperplasia of airway smooth muscle cells.
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