Curcumol inhibits PDGF-BB-induced proliferation and migration of airway smooth muscle cells by suppressing ERK/CREB pathway

Background Curcumol, possessing antiviral, antifungal, antimicrobial, anticancer, and anti-inflammatory properties, has been widely used in treating cancers and liver fibrosis. The aim of this study was to determine the effect of curcumol on the progression of asthma.Materials and methods Curcumol was administrated to platelet-derived growth factor (PDGF)-BB-stimulated airway smooth muscle cells (ASMCs). The proliferation of ASMCs was assessed by MTT and EdU incorporation assays. The apoptosis of ASMCs was measured by flow cytometry and Western blotting. The migration of ASMCs was evaluated by Transwell migration assay and Western blotting. The regulatory effects of curcumol on extracellular signal-regulated protein kinase (ERK)/cAMP response element-binding protein (CREB) pathway was evaluated by Western blotting.Results The proliferation and migration of ASMCs induced by PDGF-BB was suppressed, and the apoptosis of ASMCs was elevated by curcumol in a dose-dependent manner. The activation of ERK/CREB pathway induced by PDGF-BB was suppressed by curcumol.Conclusion Curcumol could suppress ERK/CREB pathway to inhibit proliferation and migration and promote apoptosis of PDGF-BB-stimulated ASMCs. These findings suggest that curcumol may act as a potential drug for asthma treatment (AU)

Overexpression of miR-155-5p Inhibits the Proliferation and Migration of IL-13-Induced Human Bronchial Smooth Muscle Cells by Suppressing TGF-β-Activated Kinase 1/MAP3K7-Binding Protein 2

PURPOSE: Molecular mechanisms leading to asthma is still ill-defined. Though the function of microRNAs (miRNAs) in asthma was previously reported, the involvement of miR-155 in important features of this disease remains unknown. The present study was designed to uncover the probable involvement of miR-155-5p in the proliferation and migration of IL-13-induced human bronchial smooth muscle cells (BSMCs) and the intrinsic regulatory mechanism. METHODS: The effects of different concentrations of IL-13 on the proliferation and migration of BSMCs as well as the expression of miR-155-5p and its predicted target transforming growth factor (TGF)-β-activated kinase 1/MAP3K7-binding protein 2 (TAB2) were investigated. The effects of miR-155-5p on the proliferation and migration of interleukin (IL)-13-induced BSMCs was determined in vitro using BSMCs transfected with miR-155 mimic/inhibitor and induced by a high concentration of IL-13. The quantitative real-time polymerase chain reaction (qRTPCR) was employed for determining the expression of miR-155-5p and TAB2. Western blotting was applied to analyze the expression of TAB2 at the protein level. Cell proliferation and migration were assessed using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and Transwell assays, respectively. RESULTS: The proliferation and migration of BSMCs were dose-dependently increased with IL-13 treatment. Contrariwise, IL-13 dose-dependently inhibited the expression of miR-155-5p in BSMCs. Mechanistic studies showed that inhibition of miR-155-5p further promoted the stimulatory effects of IL-13, whereas overexpression of miR-155 significantly inhibited these effects. In silico studies and luciferase reporter assays indicated that TAB2 was a negatively regulated miR-155-5p target. CONCLUSIONS: These results suggested that miR-155-5p-inhibit the IL-13-induced proliferation and migration of BSMCs by targeting TAB2 and that the IL-13/miR-155/TAB2 pathway could serve as a therapeutic target for pulmonary diseases, especially asthma.