Role of miR-155/COX-2/PGE2 signaling pathway in dioscin improving airway inflammation in asthmatic mice_Chinese Journal of Respiratory and Critical Care Medicine

Authors：

LIANG Min ¹ , BIAN Junmei ¹ , XIONG Shisi ¹ , LI Wan ¹ ,  JIANG Zhen ²

1. Department of Paediatrics, Tongren Hospital Affiliated to Wuhan University (the Third Hospital of Wuhan), Wuhan, Hubei 430074, P. R. China;
2. Wuhan Ninth Hospital, Wuhan, Hubei 430074, P. R. China;

Corresponding author：

JIANG Zhen, Email: 1637621742@qq.com

Keywords：

Dioscin; asthma; airway inflammation; microRNA-155; cyclooxygenase 2/prostaglandin E2

DOI：

10.7507/1671-6205.202111005

Video：

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Abstract Full text Figures/Tables Video References Cited by

Objective To explore the effects of dioscin (Dio) on airway inflammation and microRNA-155 (miR-155)/cyclooxygenase 2 (COX-2)/prostaglandin E2 (PGE2) pathways in asthmatic mice. Methods Seventy mice were randomly divided into control group, model group, inhibitor negative control group (inhibitor-NC group), miR-155 inhibitor group, and Dio group, Dio+miR-155 mimic negative control group (Dio+mimic-NC group), Dio+miR-155 mimic group, with 10 mice in each group. Using house dust mite to induce the preparation of asthma mouse models; enzyme linked immunosorbent assay was used to detect the levels of PGE2, tumor necrosis factor α (TNF-α), cysteyl leukotrienes (CysLTs), cysteyl leukotriene receptor 1 (CysLTR1) and interleukin (IL)-4, IL-5, IL-13 in mouse bronchoalveolar lavage fluid (BALF); hematoxylin-eosin and periodic acid-Schiff staining were used to observe the infiltration of inflammatory cells around the airway and the secretion of mucus by goblet cells; quantitative real-time PCR was used to detect the expression levels of miR-155 and COX-2 mRNA in mouse lung tissue; Western blot was used detect the expression of COX-2 protein in mouse lung tissue. Results MiR-155 inhibitor and Dio could reduce the levels of PGE2, TNF-α, CysLTs, CysLTR1 and IL-4, IL-5, IL-13 in BALF of asthmatic mice, reduce lung tissue inflammatory cell infiltration and goblet cell mucus secretion, and reduce lung tissue miR-155, COX-2 mRNA and protein expression; and miR-155 mimic could significantly weaken the anti-asthma effect of Dio. Conclusion The anti-asthma effect of Dio may be related to the inhibition of miR-155/COX-2/PGE2 pathway to reduce airway inflammation in asthmatic mice.

Citation： LIANG Min, BIAN Junmei, XIONG Shisi, LI Wan, JIANG Zhen. Role of miR-155/COX-2/PGE2 signaling pathway in dioscin improving airway inflammation in asthmatic mice. Chinese Journal of Respiratory and Critical Care Medicine, 2022, 21(11): 790-796. doi: 10.7507/1671-6205.202111005 Copy

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3.	欧国春, 陈小菊, 陈永, 等. Maresin-1对哮喘小鼠肺部炎症及MAPK信号通路的影响. 中国呼吸与危重监护杂志, 2020, 19(3): 234-239.
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6.	Kim HJ, Park SO, Byeon HW, et al. T cell-intrinsic miR-155 is required for Th2 and Th17-biased responses in acute and chronic airway inflammation by targeting several different transcription factors. Immunology, 2022, 166(3): 357-379.
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11.	Song SS, Chu L, Liang HF, et al. Protective effects of dioscin against doxorubicin-induced hepatotoxicity via regulation of Sirt1/FOXO1/NF-κb signal. Front Pharmacol, 2019, 10(1): 1030.
12.	武利娟, 韦慧玲, 仝怡宁. 薯蓣皂苷减轻卵清蛋白诱导的过敏性哮喘小鼠的气道炎症. 免疫学杂志, 2021, 37(3): 210-216.
13.	金霏, 梁秋实, 陈克研, 等. 薯蓣皂苷抑制ERK/p38MAPK信号通路减轻过敏性哮喘小鼠炎症反应. 解剖科学进展, 2020, 26(4): 400-403.
14.	Wu ZL, Wang J. Dioscin attenuates bleomycin-induced acute lung injury via inhibiting the inflammatory response in mice. Exp Lung Res, 2019, 45(8): 236-244.
15.	王思齐, 包凯帆, 王晓钰, 等. 抗生素呼吸道给药加重小鼠过敏性哮喘模型的建立. 中国比较医学杂志, 2019, 29(8): 37-43.
16.	杨勤军, 王心恒, 杨程, 等. 麻芍平喘汤对哮喘大鼠气道重塑和气道炎症及肺组织TGF-β1、Muc5AC蛋白表达的影响. 中药药理与临床, 2020, 36(5): 154-159, 64.
17.	胡蔚, 李岚. 枇杷叶提取物对卵清蛋白诱导的哮喘小鼠气道炎症和气道重塑的影响. 中国现代应用药学, 2021, 38(1): 20-27.
18.	Teng FZ, Ma XD, Cui J, et al. Acupoint catgut-embedding therapy inhibits NF-κB/COX-2 pathway in an ovalbumin-induced mouse model of allergic asthma. Biomed Res Int, 2022, 2022: 1764104.
19.	Lee SY, Kim MH, Kim SH, et al. Korean Red Ginseng affects ovalbumin-induced asthma by modulating IL-12, IL-4, and IL-6 levels and the NF-κB/COX-2 and PGE₂ pathways. J Ginseng Res, 2021, 45(4): 482-489.
20.	Gao YH, Zhao CY, Wang W, et al. Prostaglandins E2 signal mediated by receptor subtype EP2 promotes IgE production in vivo and contributes to asthma development. Sci Rep, 2016, 6(1): 20505.
21.	Zhang YM, Tao XF, Yin LH, et al. Protective effects of dioscin against cisplatin-induced nephrotoxicity via the microRNA-34a/sirtuin 1 signalling pathway. Br J Pharmacol, 2017, 174(15): 2512-2527.
22.	Urbano A, Plaza J, Turon S, et al. Transgenic mice overexpressing the PGE₂ receptor EP₂ on mast cells exhibit a protective phenotype in a model of allergic asthma. Allergy, 2021, 76(10): 3196-3199.
23.	Michael JV, Gavrila A, Nayak AP, et al. Cooperativity of E-prostanoid receptor subtypes in regulating signaling and growth inhibition in human airway smooth muscle. FASEB J, 2019, 33(4): 4780-4789.

1. Cevhertas L, Ogulur I, Maurer DJ, et al. Advances and recent developments in asthma in 2020. Allergy, 2020, 75(12): 3124-3146.
2. 朱敏, 赵丽敏, 王培, 等. 异鼠李素抑制卵清蛋白诱导的哮喘小鼠肺部炎症. 中国病理生理杂志, 2021, 37(1): 106-111.
3. 欧国春, 陈小菊, 陈永, 等. Maresin-1对哮喘小鼠肺部炎症及MAPK信号通路的影响. 中国呼吸与危重监护杂志, 2020, 19(3): 234-239.
4. Rodrigo-Muñoz JM, Gil-Martínez M, Lorente-Sorolla C, et al. miR-144-3p is a biomarker related to severe corticosteroid-dependent asthma. Front Immunol, 2022, 13(1): 858722.
5. Wu WL, Gao JL, Chen D, et al. Epithelial microRNA-30a-3p targets RUNX2/HMGB1 axis to suppress airway eosinophilic inflammation in asthma. Respir Res, 2022, 23(1): 17.
6. Kim HJ, Park SO, Byeon HW, et al. T cell-intrinsic miR-155 is required for Th2 and Th17-biased responses in acute and chronic airway inflammation by targeting several different transcription factors. Immunology, 2022, 166(3): 357-379.
7. Li L, Shan WQ, Zhu HJ, et al. SJMHE1 peptide from schistosoma japonicum inhibits asthma in mice by regulating Th17/Treg cell balance via miR-155. J Inflamm Res, 2021, 14(1): 5305-5318.
8. Qiu LP, Zhang Y, Do DC, et al. miR-155 modulates cockroach allergen- and oxidative stress-induced cyclooxygenase-2 in asthma. J Immunol, 2018, 201(3): 916-929.
9. Comer BS, Camoretti-Mercado B, Kogut PC, et al. Cyclooxygenase-2 and microRNA-155 expression are elevated in asthmatic airway smooth muscle cells. Am J Respir Cell Mol Biol, 2015, 52(4): 438-447.
10. 周好好, 黄翠萍. 支气管哮喘小鼠肺组织miR-155的变化及对环氧合酶-2的影响. 国际呼吸杂志, 2019, 39(11): 807-813.
11. Song SS, Chu L, Liang HF, et al. Protective effects of dioscin against doxorubicin-induced hepatotoxicity via regulation of Sirt1/FOXO1/NF-κb signal. Front Pharmacol, 2019, 10(1): 1030.
12. 武利娟, 韦慧玲, 仝怡宁. 薯蓣皂苷减轻卵清蛋白诱导的过敏性哮喘小鼠的气道炎症. 免疫学杂志, 2021, 37(3): 210-216.
13. 金霏, 梁秋实, 陈克研, 等. 薯蓣皂苷抑制ERK/p38MAPK信号通路减轻过敏性哮喘小鼠炎症反应. 解剖科学进展, 2020, 26(4): 400-403.
14. Wu ZL, Wang J. Dioscin attenuates bleomycin-induced acute lung injury via inhibiting the inflammatory response in mice. Exp Lung Res, 2019, 45(8): 236-244.
15. 王思齐, 包凯帆, 王晓钰, 等. 抗生素呼吸道给药加重小鼠过敏性哮喘模型的建立. 中国比较医学杂志, 2019, 29(8): 37-43.
16. 杨勤军, 王心恒, 杨程, 等. 麻芍平喘汤对哮喘大鼠气道重塑和气道炎症及肺组织TGF-β1、Muc5AC蛋白表达的影响. 中药药理与临床, 2020, 36(5): 154-159, 64.
17. 胡蔚, 李岚. 枇杷叶提取物对卵清蛋白诱导的哮喘小鼠气道炎症和气道重塑的影响. 中国现代应用药学, 2021, 38(1): 20-27.
18. Teng FZ, Ma XD, Cui J, et al. Acupoint catgut-embedding therapy inhibits NF-κB/COX-2 pathway in an ovalbumin-induced mouse model of allergic asthma. Biomed Res Int, 2022, 2022: 1764104.
19. Lee SY, Kim MH, Kim SH, et al. Korean Red Ginseng affects ovalbumin-induced asthma by modulating IL-12, IL-4, and IL-6 levels and the NF-κB/COX-2 and PGE₂ pathways. J Ginseng Res, 2021, 45(4): 482-489.
20. Gao YH, Zhao CY, Wang W, et al. Prostaglandins E2 signal mediated by receptor subtype EP2 promotes IgE production in vivo and contributes to asthma development. Sci Rep, 2016, 6(1): 20505.
21. Zhang YM, Tao XF, Yin LH, et al. Protective effects of dioscin against cisplatin-induced nephrotoxicity via the microRNA-34a/sirtuin 1 signalling pathway. Br J Pharmacol, 2017, 174(15): 2512-2527.
22. Urbano A, Plaza J, Turon S, et al. Transgenic mice overexpressing the PGE₂ receptor EP₂ on mast cells exhibit a protective phenotype in a model of allergic asthma. Allergy, 2021, 76(10): 3196-3199.
23. Michael JV, Gavrila A, Nayak AP, et al. Cooperativity of E-prostanoid receptor subtypes in regulating signaling and growth inhibition in human airway smooth muscle. FASEB J, 2019, 33(4): 4780-4789.

Chinese Journal of Respiratory and Critical Care Medicine

Role of miR-155/COX-2/PGE2 signaling pathway in dioscin improving airway inflammation in asthmatic mice

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