Source: International Congress 2014 – Cell biology 2014
Disease area: Airway diseases

Abstract

Background: Airway smooth muscle cell (ASMC) proliferation is a central feature of asthmatic airways and is elicited by mechanisms of considerable interest. The role of the phosphoinositide 3-kinase (PI3K) and the extracellular signal-regulated kinase (ERK) pathway in ASMC proliferation is well established, but it remains unclear how the c-jun N-terminal kinase (JNK) and p38 mitogen-activated protein kinase (MAPK) pathways contribute. Nuclear factor-kappa B (NF-kB) plays a well-recognized role in airway inflammation such as asthma, but there are still open questions about its role in ASMC proliferation.Objective: We sought to determine the roles of JNK, p38, and NF-kB in ASMC proliferation.Methods: Normal human bronchial airway smooth muscle cells (BSMCs), asthmatic human bronchial airway smooth muscle cells (DBSMC-Ass), and rat airway smooth muscle cells (rat ASMCs) were cultured in vitro. The effect of JNK, p38, or NF-kB inhibition on ASMC proliferation in response to fetal bovine serum (FBS) was estimated by crystal violet assay and tritiated thymidine uptake. The involvement of cell cycle regulators was examined using real-time quantitative PCR and Western blotting.Results: The inhibition of JNK by both chemical inhibitor and small interfering RNA (siRNA) strongly suppressed FBS-induced proliferation in BSMCs, DBSMC-Ass, and rat ASMCs. The p38 and NF-kB inhibitors, however, had little effect. The JNK inhibitor significantly decreased cyclin D1 protein levels in human ASMCs without significantly changing the level of cyclin D1 mRNA.Conclusion: The JNK pathway contributes to FBS-induced human ASMC proliferation, at least in part, via the regulation of cyclin D1.

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S. Chiba, Y. Sumi, K. Okayasu, T. Okamoto, T. Tateishi, H. Furusawa, K. Tsuchiya, T. Fujie, M. Tamaoka, H. Sakashita, Y. Miyazaki, N. Inase (Tokyo, Japan). The c-jun N-terminal kinase signaling pathway regulates airway smooth muscle cell proliferation. Eur Respir J 2014; 44: Suppl. 58, 3847

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