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- W2898869414 abstract "The P2X4 receptor (P2X4R) contributes to airway inflammation and airway remodeling in mice with allergic asthma. However, the molecular mechanism by which P2X4R affects the airway remodeling in allergic asthma remains largely unknown. We established an allergic asthma model by ovalbumin (OVA) inhalation in BALB/c mice. Compared with the mice in the control group, the expression of proliferating cell nuclear antigen (PCNA) increased and that of alpha-smooth muscle actin (α-SMA) decreased in the OVA-challenged mice. 5-BDBD, a P2X4R antagonist, alleviated the OVA-induced changes. To clarify the role of P2X4R in the phenotype switching of the bronchial smooth muscle, bronchial smooth muscle contractility and p38MAPK expression were investigated. Platelet-derived growth factor-BB (PDGF-BB) was used to activate the proliferation of primary-cultured rat bronchial smooth muscle cells (BSMCs). P2X4R, p38MAPK, and phenotype markers were evaluated using Western blotting or immunofluorescence. PDGF-BB administration increased the P2X4R and phospho-p38MAPK expression in BSMCs, and the increased phospho-p38MAPK expression was downregulated by silencing of the P2X4R mRNA. PDGF-BB stimulated the proliferation and synthetic phenotype of BSMCs, which was aggravated by a P2X4R agonist and alleviated by a P2X4R antagonist or silencing the P2X4R mRNA. The decreased contractile phenotype induced by PDGF-BB was alleviated by a P2X4R antagonist or by silencing the P2X4R mRNA. SB203580, p38MAPK inhibitor, inhibited the PDGF-BB-induced increasing of synthetic phenotype and the proliferation of BSMCs. These findings indicate that P2X4R acts directly on the phenotype switching of BSMCs. Inhibiting P2X4R can promote the contractile differentiation of BSMCs via p38MAPK signaling. Thus, the effect of P2X4R on airway remodeling indicates that this receptor could be a target for future drug candidates." @default.
- W2898869414 created "2018-11-09" @default.
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- W2898869414 date "2018-11-01" @default.
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- W2898869414 title "P2X4R promotes airway remodeling by acting on the phenotype switching of bronchial smooth muscle cells in rats" @default.
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- W2898869414 doi "https://doi.org/10.1007/s11302-018-9625-4" @default.
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