Bing Wei1, Mingwei Sun2, Yunxiao Shang3, Chao Zhang1, Xuyong Jiao1. 1. Department of Pediatrics, General Hospital of Shenyang Military Area Command, Shenyang 110016, China. 2. Department of First Clinical Medicine, China Medical University, Shenyang 110122, China. 3. Department of Pediatrics, Shengjing Hospital of China Medical University, Shenyang 110004, China.
Abstract
BACKGROUND: Airway remodelling is a major contributor to hyper-responsiveness leading to chronic asthma; however, the underlying mechanisms remain unclear. This study aimed to investigate the effects of a neurokinin 1 receptor (NK1R) antagonist (WIN62577) on the migration of airway smooth muscle cells (ASMCs) and the expression of NK1R and alpha-tubulin in airway remodelling using young rats with asthma. METHODS: Sprague-Dawley rats were randomly divided into a control group and airway remodelling group. Rats in the model group were stimulated with ovalbumin for 8 weeks. Primary ASMCs were cultured and purified from all rats, and then treated with different doses of WIN62577. The expression of NK1R and α-tubulin in ASMCs was assessed using immunofluorescence, real-time quantitative polymerase chain reaction, and western blotting. Changes in ASMC migration were detected by a transwell chamber assay. RESULTS: The transwell assay showed that the number of migrating ASMCs in the asthmatic airway remodelling group was significantly greater than that in the control group (P<0.01), which was inhibited by WIN62577 in a dose-dependent manner, with peak inhibition detected at 10-8 mol/L. The mRNA and protein expression levels of NK1R and α-tubulin were significantly higher in the asthmatic airway remodelling group than in the control group (P<0.05 and P<0.01, respectively), and were significantly decreased after treatment with WIN62577 (P<0.01 and P<0.05, respectively). CONCLUSIONS: NK1R antagonists may suppress ASMC migration in a rat model of airway remodelling by inhibiting tubulin expression, indicating a new potential target for the treatment and control of chronic asthma.
BACKGROUND: Airway remodelling is a major contributor to hyper-responsiveness leading to chronic asthma; however, the underlying mechanisms remain unclear. This study aimed to investigate the effects of a neurokinin 1 receptor (NK1R) antagonist (WIN62577) on the migration of airway smooth muscle cells (ASMCs) and the expression of NK1R and alpha-tubulin in airway remodelling using young rats with asthma. METHODS: Sprague-Dawley rats were randomly divided into a control group and airway remodelling group. Rats in the model group were stimulated with ovalbumin for 8 weeks. Primary ASMCs were cultured and purified from all rats, and then treated with different doses of WIN62577. The expression of NK1R and α-tubulin in ASMCs was assessed using immunofluorescence, real-time quantitative polymerase chain reaction, and western blotting. Changes in ASMC migration were detected by a transwell chamber assay. RESULTS: The transwell assay showed that the number of migrating ASMCs in the asthmatic airway remodelling group was significantly greater than that in the control group (P<0.01), which was inhibited by WIN62577 in a dose-dependent manner, with peak inhibition detected at 10-8 mol/L. The mRNA and protein expression levels of NK1R and α-tubulin were significantly higher in the asthmatic airway remodelling group than in the control group (P<0.05 and P<0.01, respectively), and were significantly decreased after treatment with WIN62577 (P<0.01 and P<0.05, respectively). CONCLUSIONS: NK1R antagonists may suppress ASMC migration in a rat model of airway remodelling by inhibiting tubulin expression, indicating a new potential target for the treatment and control of chronic asthma.
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