Effect of sanguinarine on biomechanics of rat airway smooth muscle cells_Journal of Biomedical Engineering

Authors：

LUO Mingzhi ¹ , YU Peili ¹ , JIN Yang ² , LIU Lei ¹ , LI Jingjing ¹ , PAN Yan ¹ ,  DENG Linhong ¹

1. Changzhou Key Laboratory of Respiratory Medical Engineering, Institute of Biomedical Engineering and Health Sciences, Changzhou University, Changzhou, Jiangsu 213164, P.R.China;
2. Bioengineering College, Chongqing University, Chongqing 400044, P.R.China;

Corresponding author：

DENG Linhong, Email: dlh@cczu.edu.cn

Keywords：

airway smooth muscle cells; sanguinarine; biomechanics; cell stiffness; cell traction force

DOI：

10.7507/1001-5515.201708025

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This study aimed to evaluate the effect of sanguinarine on biomechanical properties of rat airway smooth muscle cells (rASMCs) including stiffness, traction force and cytoskeletal stress fiber organization. To do so, rASMCs cultured in vitro were treated with sanguinarine solution at different concentrations (0.005~5 μmol/L) for 12 h, 24 h, 36 h, and 48 h, respectively. Subsequently, the cells were tested for their viability, stiffness, traction force, migration and microfilament distribution by using methylthiazolyldiphenyl-tetrazolium bromide assay, optical magnetic twisting cytometry, Fourier transform traction microscopy, scratch wound healing method, and immunofluorescence microscopy, respectively. The results showed that at concentration below 0.5 μmol/L sanguinarine had no effect on cell viability, but caused dose and time dependent effect on cell biomechanics. Specifically, rASMCs treated with sanguinarine at 0.05 μmol/L and 0.5 μmol/L for 12 and 24 h exhibited significant reduction in stiffness, traction force and migration speed, together with disorganization of the cytoskeletal stress fibers. Considering the essential role of airway smooth muscle cells (ASMCs) biomechanics in the airway hyperresponsiveness (AHR) of asthma, these findings suggest that sanguinarine may ameliorate AHR via alteration of ASMCs biomechanical properties, thus providing a novel approach for asthma drug development.

Citation： LUO Mingzhi, YU Peili, JIN Yang, LIU Lei, LI Jingjing, PAN Yan, DENG Linhong. Effect of sanguinarine on biomechanics of rat airway smooth muscle cells. Journal of Biomedical Engineering, 2018, 35(4): 583-591. doi: 10.7507/1001-5515.201708025 Copy

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2.	Rydell-Törmänen K, Risse P A, Kanabar V, et al. Smooth muscle in tissue remodeling and hyper-reactivity: airways and arteries. Pulm Pharmacol Ther, 2013, 26(1): 13-23.
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5.	Ozier A, Allard B, Bara I, et al. The pivotal role of airway smooth muscle in asthma pathophysiology. J Allergy (Cairo), 2011: 742710.
6.	Affonce D A, Lutchen K R. New perspectives on the mechanical basis for airway hyperreactivity and airway hypersensitivity in asthma. J Appl Physiol (1985), 2006, 101(6): 1710-1719.
7.	Janssen L J. Airway smooth muscle as a target in asthma and the beneficial effects of bronchial thermoplasty. J Allergy (Cairo), 2012: 593784.
8.	Camoretti-Mercado B. Targeting the airway smooth muscle for asthma treatment. Transl Res, 2009, 154(4): 165-174.
9.	Zuyderduyn S, Sukkar M B, Fust A, et al. Treating asthma means treating airway smooth muscle cells. Eur Respir J, 2008, 32(2): 265-274.
10.	Stephens N L, Li Weilong, Jiang He, et al. The biophysics of asthmatic airway smooth muscle. Respir Physiol Neurobiol, 2003, 137(2/3): 125-140.
11.	Black J L, Panettieri R A, Banerjee A, et al. Airway smooth muscle in asthma: just a target for bronchodilation?. Clin Chest Med, 2012, 33(3): 543-558.
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14.	Trepat X, DENG Linhong, An S S, et al. Universal physical responses to stretch in the living cell. Nature, 2007, 447(7144): 592-595.
15.	Rosner S R, Pascoe C D, Blankman E, et al. The actin regulator zyxin reinforces airway smooth muscle and accumulates in airways of fatal asthmatics. PLoS One, 2017, 12(3): e0171728.
16.	Deshpande D A, Wang W C H, Mcilmoyle E L, et al. Bitter taste receptors on airway smooth muscle bronchodilate by a localized Calcium flux and reverse obstruction. Nat Med, 2010, 16(11): 1299-1304.
17.	Park C Y, Zhou E H, Tambe D, et al. High-throughput screening for modulators of cellular contractile force. Integr Biol (Camb), 2015, 7(10): 1318-1324.
18.	Hu C M, Cheng H W, Cheng Y W, et al. Mechanisms underlying the induction of vasorelaxation in rat thoracic aorta by sanguinarine. Jpn J Pharmacol, 2001, 85(1): 47-53.
19.	王慧, 王悦尚, 刘兆颖, 等. 血根碱对大鼠肠平滑肌细胞收缩的抑制作用. 湖南农业大学学报:自然科学版, 2012, 38(05): 519-525.
20.	Wang Hui, Yin G, Yu Chunhong, et al. Inhibitory effect of sanguinarine on PKC-CPI-17 pathway mediating by muscarinic receptors in dispersed intestinal smooth muscle cells. Res Vet Sci, 2013, 95(3): 1125-1133.
21.	Wang Yue, Lu Yun, Luo Mingzhi, et al. Evaluation of pharmacological relaxation effect of the natural product naringin on in vitro cultured airway smooth muscle cells and in vivo ovalbumin-induced asthma Balb/c mice. Biomedical reports, 2016, 5(6): 715-722.
22.	Zhang Ying, Ng S S, Wang Yilei, et al. Collective cell traction force analysis on aligned smooth muscle cell sheet between three-dimensional microwalls. Interface Focus, 2014, 4(2): 20130056.
23.	An S S, Fabry B, Trepat X, et al. Do biophysical properties of the airway smooth muscle in culture predict airway hyperresponsiveness?. Am J Respir Cell Mol Biol, 2006, 35(1): 55-64.
24.	Seow C Y. Passive stiffness of airway smooth muscle: the next target for improving airway distensibility and treatment for asthma?. Pulm Pharmacol Ther, 2013, 26(1): 37-41.
25.	贾海燕, 徐婉晴, 张庭华, 等. 血根碱对大鼠离体子宫平滑肌收缩的影响及其机制研究. 中国畜牧兽医, 2017, 44(07): 2209-2213.

1. Mccracken J L, Veeranki S P, Ameredes B T, et al. Diagnosis and management of asthma in adults: a review. JAMA, 2017, 318(3): 279-290.
2. Rydell-Törmänen K, Risse P A, Kanabar V, et al. Smooth muscle in tissue remodeling and hyper-reactivity: airways and arteries. Pulm Pharmacol Ther, 2013, 26(1): 13-23.
3. Chapman D G, Irvin C G. Mechanisms of airway hyper-responsiveness in asthma: the past, present and yet to come. Clinical and Experimental Allergy, 2015, 45(4): 706-719.
4. Bates J H, Maksym G N. Mechanical determinants of airways hyperresponsiveness. Crit Rev Biomed Eng, 2011, 39(4): 281-296.
5. Ozier A, Allard B, Bara I, et al. The pivotal role of airway smooth muscle in asthma pathophysiology. J Allergy (Cairo), 2011: 742710.
6. Affonce D A, Lutchen K R. New perspectives on the mechanical basis for airway hyperreactivity and airway hypersensitivity in asthma. J Appl Physiol (1985), 2006, 101(6): 1710-1719.
7. Janssen L J. Airway smooth muscle as a target in asthma and the beneficial effects of bronchial thermoplasty. J Allergy (Cairo), 2012: 593784.
8. Camoretti-Mercado B. Targeting the airway smooth muscle for asthma treatment. Transl Res, 2009, 154(4): 165-174.
9. Zuyderduyn S, Sukkar M B, Fust A, et al. Treating asthma means treating airway smooth muscle cells. Eur Respir J, 2008, 32(2): 265-274.
10. Stephens N L, Li Weilong, Jiang He, et al. The biophysics of asthmatic airway smooth muscle. Respir Physiol Neurobiol, 2003, 137(2/3): 125-140.
11. Black J L, Panettieri R A, Banerjee A, et al. Airway smooth muscle in asthma: just a target for bronchodilation?. Clin Chest Med, 2012, 33(3): 543-558.
12. Oria R, Wiegand T, Escribano J, et al. Force loading explains spatial sensing of ligands by cells. Nature, 2017, 552(7684): 219-224.
13. Dinardo C L, Santos H C, Vaquero A R, et al. Smoking and female sex: independent predictors of human vascular smooth muscle cells stiffening. PLoS One, 2015, 10(12): e0145062.
14. Trepat X, DENG Linhong, An S S, et al. Universal physical responses to stretch in the living cell. Nature, 2007, 447(7144): 592-595.
15. Rosner S R, Pascoe C D, Blankman E, et al. The actin regulator zyxin reinforces airway smooth muscle and accumulates in airways of fatal asthmatics. PLoS One, 2017, 12(3): e0171728.
16. Deshpande D A, Wang W C H, Mcilmoyle E L, et al. Bitter taste receptors on airway smooth muscle bronchodilate by a localized Calcium flux and reverse obstruction. Nat Med, 2010, 16(11): 1299-1304.
17. Park C Y, Zhou E H, Tambe D, et al. High-throughput screening for modulators of cellular contractile force. Integr Biol (Camb), 2015, 7(10): 1318-1324.
18. Hu C M, Cheng H W, Cheng Y W, et al. Mechanisms underlying the induction of vasorelaxation in rat thoracic aorta by sanguinarine. Jpn J Pharmacol, 2001, 85(1): 47-53.
19. 王慧, 王悦尚, 刘兆颖, 等. 血根碱对大鼠肠平滑肌细胞收缩的抑制作用. 湖南农业大学学报:自然科学版, 2012, 38(05): 519-525.
20. Wang Hui, Yin G, Yu Chunhong, et al. Inhibitory effect of sanguinarine on PKC-CPI-17 pathway mediating by muscarinic receptors in dispersed intestinal smooth muscle cells. Res Vet Sci, 2013, 95(3): 1125-1133.
21. Wang Yue, Lu Yun, Luo Mingzhi, et al. Evaluation of pharmacological relaxation effect of the natural product naringin on in vitro cultured airway smooth muscle cells and in vivo ovalbumin-induced asthma Balb/c mice. Biomedical reports, 2016, 5(6): 715-722.
22. Zhang Ying, Ng S S, Wang Yilei, et al. Collective cell traction force analysis on aligned smooth muscle cell sheet between three-dimensional microwalls. Interface Focus, 2014, 4(2): 20130056.
23. An S S, Fabry B, Trepat X, et al. Do biophysical properties of the airway smooth muscle in culture predict airway hyperresponsiveness?. Am J Respir Cell Mol Biol, 2006, 35(1): 55-64.
24. Seow C Y. Passive stiffness of airway smooth muscle: the next target for improving airway distensibility and treatment for asthma?. Pulm Pharmacol Ther, 2013, 26(1): 37-41.
25. 贾海燕, 徐婉晴, 张庭华, 等. 血根碱对大鼠离体子宫平滑肌收缩的影响及其机制研究. 中国畜牧兽医, 2017, 44(07): 2209-2213.

Journal of Biomedical Engineering

Effect of sanguinarine on biomechanics of rat airway smooth muscle cells

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