The inhibitory effect of resveratrol on airway remodeling in mice with chronic asthma_Chinese Journal of Respiratory and Critical Care Medicine

Authors：

HE Guangzhen , HUANG Ge , CHEN Yifei , ZHU Fangfang , YANG Jiong ,  GAO Yadong

Department of Respiratory Medicine, Zhongnan Hospital of Wuhan University, Wuhan, Hubei 430071, P.R.China;

Corresponding author：

GAO Yadong, Email: gaoyadong@whu.edu.cn

Keywords：

Asthma; Airway remodeling; Resveratrol; Mice model

DOI：

10.7507/1671-6205.201607027

Video：

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ObjectiveTo investigate the effects of resveratrol on airway remodeling in mice with chronic asthma. MethodsTwenty-four female BALB/c mice were randomly divided into three groups (8 mice in each group), namely a control group, an asthma group and a resveratrol (RV) group. All mice were sensitized with ovalbumin (OVA). The sensitized mice were then challenged with OVA while the control group were challenged with phosphate-buffered saline. The mice in the RV group were intraperitoneally injected with RV 30 min before OVA challenge, while the mice in the control and the asthma group were intraperitoneally injected with equal volume of dimethylsulfoxide. Periodic acid-Schiff (PAS) staining was performed to evaluate goblet cell hyperplasia, and Masson-trichrome staining was used to evaluate the deposition of collagen matrix. In addition, immunohistochemical analysis of the α-smooth muscle actin (α-SMA) was applied to examine airway smooth muscle cell hyperplasia and hypertrophy. The positive staining with PAS, Masson, α-SMA areas (μm ²/μm) of per bronchial basement membrane perimeter was used to indicate the degree of airway remodeling. ResultsIn the asthma group and the RV group, the degree of the goblet cell hyperplasia was significantly higher than that in the control group (5.44±1.13, 4.18±0.85vs. 0.00±0.00,P<0.01), and the level of goblet cell hyperplasia in the RV group was lower than that in the asthma group (P<0.05). The Masson staining showed that the deposition of collagen in the asthma group and the RV group was significantly higher than that in the control group (9.80±2.78, 5.71±0.68vs. 1.67±0.65,P<0.01), and the collagen deposition in the RV group was further lower than that in the asthma group (P<0.01). The α-SMA immunohistochemical analysis demonstrated that the expression of α-SMA in the asthma group and the RV group was significantly higher than that in the control group (10.39±1.65, 7.57±1.98vs. 2.41±1.06,P<0.01), and the level of α-SMA in the RV group was also lower than that in the asthma group (P<0.05). ConclusionThese findings suggest that resveratrol has an inhibitory effect on the process of airway remodeling in mice with chronic asthma.

Citation： HE Guangzhen, HUANG Ge, CHEN Yifei, ZHU Fangfang, YANG Jiong, GAO Yadong. The inhibitory effect of resveratrol on airway remodeling in mice with chronic asthma. Chinese Journal of Respiratory and Critical Care Medicine, 2017, 16(3): 223-227. doi: 10.7507/1671-6205.201607027 Copy

1.	Holtzman MJ, Byers DE, Benoit LA, et al. Immune pathways for translating viral infection into chronic airway disease. Adv Immunol, 2009, 102(9): 245-276.
2.	Locksley RM. Asthma and allergic inflammation. Cell, 2010, 140(6): 777-783.
3.	Walter MJ, Holtzman MJ. A centennial history of research on asthma pathogenesis. Am J Respir Cell Mol Biol, 2005, 32(6): 483-489.
4.	Holgate ST. Pathogenesis of asthma. Clin Exp Allergy, 2008, 38(6): 872-897.
5.	Kumar V, Pandey A, Jahan S, et al. Differential responses of Trans-Resveratrol on proliferation of neural progenitor cells and aged rat hippocampal neurogenesis. Sci Rep, 2016, 6: 28142.
6.	Lee M, Kim S, Kwon OK, et al. Anti-inflammatory and anti-asthmatic effects of resveratrol, a polyphenolic stilbene, in a mouse model of allergic asthma. Int Immunopharmacol, 2009, 9(4): 418-424.
7.	Aich J, Mabalirajan U, Ahmad T, et al. Resveratrol attenuates experimental allergic asthma in mice by restoring inositol polyphosphate 4 phosphatase (INPP4A). Int Immunopharmacol, 2012, 14(4): 438-443.
8.	Ni ZH, Tang JH, Chen G, et al. Resveratrol inhibits mucus overproduction and MUC5AC expression in a murine model of asthma. Mol Med Rep, 2016, 13(1): 287-294.
9.	Wei G, Chen X, Wang G, et al. Effect of resveratrol on the prevention of intra-abdominal adhesion formation in a rat model. Cell Physiol Biochem, 2016, 39(1): 33-46.
10.	Chang YC, Lin CW, Yu CC, et al. Resveratrol suppresses myofibroblast activity of human buccal mucosal fibroblasts through the ep IgE netic inhibition of ZEB1 expression. Oncotarget, 2016, 7(11): 12137-12149.
11.	Raj P, Aloud BM, Louis XL, et al. Resveratrol is equipotent to perindopril in attenuating post-infarct cardiac remodeling and contractile dysfunction in rats. J Nutr Biochem, 2016, 28: 155-163.
12.	Ma Y, Ge A, Zhu W, et al. Morin attenuates ovalbumin-induced airway inflammation by modulating oxidative stress-responsive MAPK signaling. Oxid Med Cell Longev, 2016: 5843672. Available at: https://www.hindawi.com/journals/omcl/2016/5843672/.
13.	Royce SG, Shen M, Patel KP, et al. Mesenchymal stem cells and serelaxin synergistically abrogate established airway fibrosis in an experimental model of chronic allergic airways disease. Stem Cell Res, 2015,15(3): 495-505.
14.	朱涛, 任旭斌, 朱静, 等. γ-氨基丁酸 A 型受体调节哮喘动物模型气道重构的实验研究. 南方医科大学学报, 2010, 30(4): 842-846.
15.	Zhu T, Zhang W, Wang DX, et al. Rosuvastatin attenuates mucus secretion in a murine model of chronic asthma by inhibiting the gamma-aminobutyric acid type A receptor. Chin Med J (Engl), 2012, 125(8): 1457-1464.
16.	Ren Y, Su XM, Kong LF, et al. Therapeutic effects of histone deacetylase inhibitors in a murine asthma model. Inflamm Res, 2016,65(12): 995-1008.
17.	Collison A, Li J, Pereira De Siqueira A, et al. Tumor necrosis factor-related apoptosis-inducing ligand regulates hallmark features of airways remodeling in allergic airways disease. Am J Respir Cell and Mol Biol, 2014,51(1): 86-93.
18.	Difazio RM, Mattila JT, Klein EC, et al. Active transforming growth factor-β is associated with phenotypic changes in granulomas after drug treatment in pulmonary tuberculosis. Fibrogenesis Tissue Repair, 2016, 9: 6.
19.	Mamalis A, Jagdeo J. The combination of resveratrol and high-fluence light emitting diode-red light produces synergistic photobotanical inhibition of fibroblast proliferation and collagen synthesis: a novel treatment for skin fibrosis. Dermatol Surg, 2017, 43(1): 81-86.
20.	Fagone E, Conte E, Gili, E, et al. Resveratrol inhibits transforming growth factor-β-induced proliferation and differentiation of ex vivo human lung fibroblasts into myofibroblasts through ERK/Akt inhibition and PTEN restoration. Exp Lung Res, 2011,3(37): 162-174.
21.	Shi Y, Xu X, Tan Y, et al. A liver-X-receptor ligand, T0901317, attenuates IgE production and airway remodeling in chronic asthma model of mice. PLos One, 2014, 3(9): e92668.
22.	Gao YD, Zou JJ, Zheng JW, et al. Promoting effects of IL-13 on Ca²⁺ release and store-operated Ca²⁺ entry in airway smooth muscle cells. Pulm Pharmacol Ther, 2010, 23(3): 182-189.
23.	黄革, 钟金男, 何光珍, 等. cAMP 直接激活的交换蛋白在哮喘小鼠气道重塑中的作用. 武汉大学学报(医学版), 2016, 37(1): 20-24.
24.	Cheung TM, Ganatra MP,Truskey GA, et al. Effect of cellular senescence on the albumin permeability of blood-derived endothelial cells. Am J Physiol Heart Circ Physiol, 2012, 303(11): H1374-H1383.
25.	Chen JX, Zhou H, Wang JL, et al. Therapeutic effects of resveratrol in a mouse model of HDM-induced allergic asthma. Int Immunopharmacol, 2015, 25(1): 43-48.

1. Holtzman MJ, Byers DE, Benoit LA, et al. Immune pathways for translating viral infection into chronic airway disease. Adv Immunol, 2009, 102(9): 245-276.
2. Locksley RM. Asthma and allergic inflammation. Cell, 2010, 140(6): 777-783.
3. Walter MJ, Holtzman MJ. A centennial history of research on asthma pathogenesis. Am J Respir Cell Mol Biol, 2005, 32(6): 483-489.
4. Holgate ST. Pathogenesis of asthma. Clin Exp Allergy, 2008, 38(6): 872-897.
5. Kumar V, Pandey A, Jahan S, et al. Differential responses of Trans-Resveratrol on proliferation of neural progenitor cells and aged rat hippocampal neurogenesis. Sci Rep, 2016, 6: 28142.
6. Lee M, Kim S, Kwon OK, et al. Anti-inflammatory and anti-asthmatic effects of resveratrol, a polyphenolic stilbene, in a mouse model of allergic asthma. Int Immunopharmacol, 2009, 9(4): 418-424.
7. Aich J, Mabalirajan U, Ahmad T, et al. Resveratrol attenuates experimental allergic asthma in mice by restoring inositol polyphosphate 4 phosphatase (INPP4A). Int Immunopharmacol, 2012, 14(4): 438-443.
8. Ni ZH, Tang JH, Chen G, et al. Resveratrol inhibits mucus overproduction and MUC5AC expression in a murine model of asthma. Mol Med Rep, 2016, 13(1): 287-294.
9. Wei G, Chen X, Wang G, et al. Effect of resveratrol on the prevention of intra-abdominal adhesion formation in a rat model. Cell Physiol Biochem, 2016, 39(1): 33-46.
10. Chang YC, Lin CW, Yu CC, et al. Resveratrol suppresses myofibroblast activity of human buccal mucosal fibroblasts through the ep IgE netic inhibition of ZEB1 expression. Oncotarget, 2016, 7(11): 12137-12149.
11. Raj P, Aloud BM, Louis XL, et al. Resveratrol is equipotent to perindopril in attenuating post-infarct cardiac remodeling and contractile dysfunction in rats. J Nutr Biochem, 2016, 28: 155-163.
12. Ma Y, Ge A, Zhu W, et al. Morin attenuates ovalbumin-induced airway inflammation by modulating oxidative stress-responsive MAPK signaling. Oxid Med Cell Longev, 2016: 5843672. Available at: https://www.hindawi.com/journals/omcl/2016/5843672/.
13. Royce SG, Shen M, Patel KP, et al. Mesenchymal stem cells and serelaxin synergistically abrogate established airway fibrosis in an experimental model of chronic allergic airways disease. Stem Cell Res, 2015,15(3): 495-505.
14. 朱涛, 任旭斌, 朱静, 等. γ-氨基丁酸 A 型受体调节哮喘动物模型气道重构的实验研究. 南方医科大学学报, 2010, 30(4): 842-846.
15. Zhu T, Zhang W, Wang DX, et al. Rosuvastatin attenuates mucus secretion in a murine model of chronic asthma by inhibiting the gamma-aminobutyric acid type A receptor. Chin Med J (Engl), 2012, 125(8): 1457-1464.
16. Ren Y, Su XM, Kong LF, et al. Therapeutic effects of histone deacetylase inhibitors in a murine asthma model. Inflamm Res, 2016,65(12): 995-1008.
17. Collison A, Li J, Pereira De Siqueira A, et al. Tumor necrosis factor-related apoptosis-inducing ligand regulates hallmark features of airways remodeling in allergic airways disease. Am J Respir Cell and Mol Biol, 2014,51(1): 86-93.
18. Difazio RM, Mattila JT, Klein EC, et al. Active transforming growth factor-β is associated with phenotypic changes in granulomas after drug treatment in pulmonary tuberculosis. Fibrogenesis Tissue Repair, 2016, 9: 6.
19. Mamalis A, Jagdeo J. The combination of resveratrol and high-fluence light emitting diode-red light produces synergistic photobotanical inhibition of fibroblast proliferation and collagen synthesis: a novel treatment for skin fibrosis. Dermatol Surg, 2017, 43(1): 81-86.
20. Fagone E, Conte E, Gili, E, et al. Resveratrol inhibits transforming growth factor-β-induced proliferation and differentiation of ex vivo human lung fibroblasts into myofibroblasts through ERK/Akt inhibition and PTEN restoration. Exp Lung Res, 2011,3(37): 162-174.
21. Shi Y, Xu X, Tan Y, et al. A liver-X-receptor ligand, T0901317, attenuates IgE production and airway remodeling in chronic asthma model of mice. PLos One, 2014, 3(9): e92668.
22. Gao YD, Zou JJ, Zheng JW, et al. Promoting effects of IL-13 on Ca²⁺ release and store-operated Ca²⁺ entry in airway smooth muscle cells. Pulm Pharmacol Ther, 2010, 23(3): 182-189.
23. 黄革, 钟金男, 何光珍, 等. cAMP 直接激活的交换蛋白在哮喘小鼠气道重塑中的作用. 武汉大学学报(医学版), 2016, 37(1): 20-24.
24. Cheung TM, Ganatra MP,Truskey GA, et al. Effect of cellular senescence on the albumin permeability of blood-derived endothelial cells. Am J Physiol Heart Circ Physiol, 2012, 303(11): H1374-H1383.
25. Chen JX, Zhou H, Wang JL, et al. Therapeutic effects of resveratrol in a mouse model of HDM-induced allergic asthma. Int Immunopharmacol, 2015, 25(1): 43-48.

Chinese Journal of Respiratory and Critical Care Medicine

The inhibitory effect of resveratrol on airway remodeling in mice with chronic asthma

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