Dexmedetomidine represses TGF-ß1-induced extracellular matrix production and proliferation of airway smooth muscle cells by inhibiting MAPK signaling pathway.

BACKGROUND: Airway remodeling is implicated in the pathogenesis of asthma, and abnormal proliferation of airway smooth muscle cells (ASMCs) contribute to airway remodeling. Inflammatory mediator, transforming growth factor-ß1 (TGF-ß1), stimulates the proliferation of ASMCs, and is associated with airway remodeling in asthma. Dexmedetomidine (DEX) has been widely used in the adjuvant therapy of acute asthma. OBJECTIVE: The potential effects of DEX on extracellular matrix (ECM) production and proliferation of ASMCs were investigated in this study. MATERIAL AND METHODS: Human ASMCs were incubated with TGF-ß1 for 48 hours, and then treated with different concentrations of DEX for another 24 hours. Cell proliferation was detected by MTT and BrdU (5'-bromo-2'-deoxyuridine) staining. Flow cytometry was used to assess cell apoptosis, and western blot was applied to identify the underlying mechanism. RESULTS: TGF-ß1 induced increase in cell viability and bromodeoxyuridine (BrdU) positive cells in ASMCs while repressed cell apoptosis. Second, TGF-ß1-induced ASMCs were then treated with different concentrations of DEX. Cell viability of TGF-ß1-induced ASMCs was decreased by incubation of DEX. The number of BrdU positive cells in TGF-ß1-induced ASMCs was reduced by incubation of DEX. Moreover, incubation of DEX promoted cell apoptosis of TGF-ß1-induced ASMCs. Third, incubation of DEX attenuated TGF-ß1-induced increase in fibronectin, collagen I, MMP9, and versican in ASMCs. Lastly, the up-regulation of phosphorylated extracellular receptor kinase (p-ERK), phosphorylated Jun N-terminal Kinase (p-JNK), and p-p38 in TGF-ß1-induced ASMCs was reversed by incubation of DEX. CONCLUSION: DEX suppressed TGF-ß1-induced ECM production and proliferation of ASMCs through inactivation of p38 mitogen-activated protein kinase (MAPK) pathway, providing a potential strategy for prevention of asthma.