Original Articles

Effect of Xuanfei Tongqiao acupuncture on nasal inflammation in rats with allergic rhinitis: modulation of long non-coding RNA growth arrest-specific transcript 5 methylation modification

  • Hequn LYU ,
  • Chunli ZENG ,
  • Hanrui ZHANG ,
  • Chen YANG ,
  • Yan SHEN ,
  • Yongjun PENG
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  • 1 Department of Acupuncture and Rehabilitation, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing 210029, China
    2 Department of Acupuncture, Yancheng TCM Hospital Affiliated to Nanjing University of Chinese Medicine, Yancheng 224000, China
    3 Department of Lung Disease, Yancheng TCM Hospital Affiliated to Nanjing University of Chinese Medicine, Yancheng 224000, China
    4 Department of Critical Care Medicine, Seventh People’s Hospital of Shanghai University of Traditional Chinese Medicine, Shanghai 200137, China
    5 Department of Acupuncture and Rehabilitation, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing 210029, China
    6 National Clinical Research Center for Chinese Medicine Acupuncture and Moxibustion, First Teaching Hospital of Tianjin University of Traditional Chinese Medicine, Tianjin 300000, China
    7 Department of Acupuncture and Rehabilitation, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing 210029, China
    8 National Clinical Research Center for Chinese Medicine Acupuncture and Moxibustion, First Teaching Hospital of Tianjin University of Traditional Chinese Medicine, Tianjin 300000, China
LYU Hequn and ZENG Chunli are co-first authors and contributed equally to this work

Received date: 2024-06-12

  Accepted date: 2024-12-30

  Online published: 2025-11-24

Supported by

Multi-Center Clinical Study on Xuanfei Tongqiao Acupuncture combined with Sphenopalatine Ganglion Stimulation in the Treatment of Allergic Rhinitis(NCRCOP2023008);Clinical Observation on Preventive Acupuncture for Seasonal Allergic Rhinitis based on the Theory of "Strong Spleen Prevents Pathogenic Invasion"(2020043);Mechanism of Xuanfei Tongqiao Acupuncture in Treating Allergic Rhinitis via m6A Methylation Modification of lncRNA GAS5(YK2023017)

Abstract

OBJECTIVE: To examine the effect of Xuanfei Tongqiao acupuncture on nasal inflammation in rats with allergic rhinitis (AR) and its underlying mechanisms, particularly focusing on the role of acupuncture in regulating the methylation of long non-coding RNA growth arrest-specific transcript 5 (lncRNA GAS5).

METHODS: Interventions involved acupuncture or short hairpin RNA-GAS5 (sh-GAS5) lentivirus in an ovalbumin-induced AR rat model. Nasal mucosal tissues were collected post-intervention for pathological analysis. Parameters assessed included the proportion of type 2 innate lymphoid cells (ILC2s), the expression of GATA binding protein 3 (GATA3), methyltransferase-like 3 (METTL3), interleukin (IL)-33 proteins, and the expression of METTL3 and lncRNA-GAS5.

RESULTS: Xuanfei Tongqiao acupuncture and/or lentivirus sh-GAS5 significantly alleviated rhinitis symptoms and reduced nasal inflammation in AR rats. This was evidenced by a reduction in inflammatory cells, eosinophils, and cuprocytes in nasal mucosal tissues, along with a decreased proportion of ILC2s. Furthermore, protein levels of GATA3, METTL3, and IL-33, as well as the expression of METTL3 and lncRNA-GAS5, were significantly reduced. These findings suggest that lncRNA-GAS5 and its N6-methyladenosine methylation are key regulators of AR inflammation, with acupuncture exerting a modulatory effect on this pathway.

CONCLUSIONS: Xuanfei Tongqiao acupuncture therapy inhibited the METTL3-GAS5-GATA3-IL-33-ILC2 pathway, reducing the inflammatory response and alleviating nasal symptoms in AR rats. These results suggest that Xuanfei Tongqiao acupuncture could serve as a potential alternative therapy for preventing and managing AR associated with inflammation.

Cite this article

Hequn LYU , Chunli ZENG , Hanrui ZHANG , Chen YANG , Yan SHEN , Yongjun PENG . Effect of Xuanfei Tongqiao acupuncture on nasal inflammation in rats with allergic rhinitis: modulation of long non-coding RNA growth arrest-specific transcript 5 methylation modification[J]. Journal of Traditional Chinese Medicine, 2025 , 45(6) : 1263 -1272 . DOI: 10.19852/j.cnki.jtcm.2025.06.007

References

1. Bro?ek JL, Bousquet J, Agache I, et al. Allergic rhinitis and its impact on asthma (ARIA) guidelines-2016 revision. J Allergy Clin Immunol 2017; 140: 950-8.
2. Luo P, Ying J, Li J, et al. Air pollution and allergic rhinitis: findings from a prospective cohort study. Environ Sci Technol 2023; 57: 15835-45.
3. Pawankar R, Akdis CA. Climate change and the epithelial barrier theory in allergic diseases: a one health approach to a green environment. Allergy 2023; 78: 2829-34.
4. Alkotob SS, Cannedy C, Harter K, et al. Advances and novel developments in environmental influences on the development of atopic diseases. Allergy 2020; 75: 3077-86.
5. Kilanowski A, Thiering E, Wang G, et al. Allergic disease trajectories up to adolescence: characteristics, early-life, and genetic determinants. Allergy 2023; 78: 836-50.
6. Huang F, Lyu XL, Jiao XF, et al. Progress of researches on acupuncture treatment of allergic rhinitis. Zhen Ci Yan Jiu 2023; 48: 153-7.
7. Ding LB, Wang HJ, Yao L, et al. Electroacupuncture stimulating Neixiyan (EX-LE5) and Dubi (ST35) alleviates osteoarthritis in rats induced by anterior cruciate ligament transaction affecting DNA methylation regulated transcription of miR-146a and miR-140-5p. J Ttradit Chin Med 2024; 43: 983-90.
8. Zhang C, Fu J, Zhou Y. A review in research progress concerning m6A methylation and immunoregulation. Front Immunol 2019; 10: 922.
9. Mj?sberg J, Bernink J, Golebski K, et al. The transcription factor GATA3 is essential for the function of human type 2 innate lymphoid cells. Immunity 2012; 37: 649-59.
10. Jiang X, Feng LC, Li LP. Expression of MAPK and NF-kappa B signaling pathway in patients with allergic rhinitis. Lab Med Clin 2018; 15: 965-6.
11. Chen J, Zhang YC, Huang C, et al. m(6)A regulates neurogenesis and neuronal development by modulating histone methyltransferase Ezh2. Genom Proteom Bioinformatics 2019; 17: 154-68.
12. Zhou J, Xiong R, Zhou J, et al. Involvement of m6A regulatory factor IGF2BP 1 in malignant transformation of human bronchial epithelial Beas-2B cells induced by tobacco carcinogen NNK. Toxicol Appl Pharmacol 2022; 436: 115849.
13. Filippova JA, Matveeva AM, Zhuravlev ES, et al. Are small nucleolar RNAs "CRISPRable"? A report on box C/D small nucleolar RNA editing in human cells. Front Pharmacol 2019; 10: 1246.
14. Shen F. Clinical effect on acupuncture of Xuan-Fei-Tong-Qiao method in allergic rhinitis and its expression on TLR2. Nanjing: Nanjing University of Chinese Medicine; 2017: 34.
15. Tonelli LH, Katz M, Kovacsics CE, et al. Allergic rhinitis induces anxiety-like behavior and altered social interaction in rodents. Brain Behav Immun 2009; 23: 784-93.
16. Yu SG, Xu B. Experimental acupuncture science. 2nd ed. Beijing: People's Medical Publishing House, 2016: 287-90.
17. Wang J, Zhou Y, Zhang H, et al. Pathogenesis of allergic diseases and implications for therapeutic interventions. Signal Transduct Target Ther 2023; 8: 138.
18. Mersha TB, Afanador Y, Johansson E, et al. Resolving clinical phenotypes into endotypes in allergy: molecular and omics approaches. Clin Rev Allergy Immunol 2021; 60: 200-19.
19. Hoyte FCL, Nelson HS. Recent advances in allergic rhinitis. F1000Res 2018; 7: F1000.
20. Li K. Case studies on the treatment of Biqiu using organ-regulating acupuncture techniques. Zhong Yi Yao Tong Bao 2022; 21: 53-5.
21. Liu YT, Lyu XD, Pang LJ, Liu C, Liu YM. Discussion of special intrinsic quality of pulmonary diseases from "The Lung Opens into Nose” . Liaoning Da Xue Xue Bao 2016; 18: 72-4.
22. Yang CY. Clinical interpretation of 70 common and important acupoints. Beijing: China Medical Science and Technology Press, 2017: 217-8.
23. Luo WJ, Chen CL, Luo BY, Yang CX, Zhang F, Cai LH. Clinical observation of the efficacy of three nasal needles combined with pecking moxibustion at Dazhui in the treatment of Qi deficiency type allergic rhinitis. Quan Qiu Zhong Yi Yao Za Zhi 2021; 14: 1340-3.
24. Bai J, Li SX, Zhang ZG, Wang JQ. Treating one case of allergic rhinitis by three nasal acupuncture plus wheat grain moxibustion. Zhong Guo Lin Chuang Yi Xue Za Zhi 2022; 14: 68-9.
25. Ma Y, Shi L, Zhao K, Zheng C. lncRNA FR215775 regulates Th2 differentiation in murine allergic rhinitis. J Immunol Res 2022; 2022: 7783481.
26. Wen S, Li F, Tang Y, et al. MIR222HG attenuates macrophage M2 polarization and allergic inflammation in allergic rhinitis by targeting the miR146a-5p/TRAF6/NF-κB axis. Front Immunol 2023; 14: 1168920.
27. Zhang H, Zhu X, Liu X, Wang Y, Liu Y. Long non-coding RNA FOXD3-AS1 regulates the expression and secretion of IL-25 in nasal epithelial cells to inhibit Th2 type immunoreaction in allergic rhinitis. Mol Cell Biochem 2020; 473: 239-46.
28. Zhao W, Yu HH, Meng WW, et al. Icariin restrains NLRP3 inflammasome-mediated Th2 immune responses and ameliorates atopic dermatitis through modulating a novel lncRNA MALAT1/miR-124-3p axis. Pharm Biol 2023; 61: 1249-59.
29. Li Y, Liu Z, Mou Y, et al. LncRNA FAM239A modulates T helper cell responses via tyrosine phosphatase SHP2 in allergic rhinitis. Allergol Int 2023; 72: 480-3.
30. Thio CLP, Chang YJ. The modulation of pulmonary group 2 innate lymphoid cell function in asthma: from inflammatory mediators to environmental and metabolic factors. Exp Mol Med 2023; 55: 1872-84.
31. Wang C, Zhuo JJ, Li WQ, Zhou ML, Cheng KJ. Role of autophagy and mitophagy of group 2 innate lymphoid cells in allergic and local allergic rhinitis. World Allergy Organ J 2024; 17: 100852.
32. Srivastava RK, Sapra L, Bhardwaj A, Mishra PK, Verma B, Baig Z. Unravelling the immunobiology of innate lymphoid cells (ILCs): implications in health and disease. Cytokine Growth Factor Rev 2023; 74: 56-75.
33. Zhong C, Zheng M, Cui K, et al. Differential expression of the transcription factor GATA3 specifies lineage and functions of innate lymphoid cells. Immunity 2020; 52: 83-95. e84.
34. Zhong Z, Huang X, Zhang S, et al. Blocking Notch signalling reverses miR-155-mediated inflammation in allergic rhinitis. Int Immunopharmacol 2023; 116: 109832.
35. Cayrol C, Duval A, Schmitt P, et al. Environmental allergens induce allergic inflammation through proteolytic maturation of IL-33. Nat Immunol 2018; 19: 375-85.
36. Hoyler T, Klose CS, Souabni A, et al. The transcription factor GATA-3 controls cell fate and maintenance of type 2 innate lymphoid cells. Immunity 2012; 37: 634-48.
37. Zhu X, Sun Y, Yu Q, Wang X, Wang Y, Zhao Y. Exosomal lncRNA GAS5 promotes M1 macrophage polarization in allergic rhinitis via restraining mTORC1/ULK1/ATG13-mediated autophagy and subsequently activating NF-кB signaling. Int Immunopharmacol 2023; 121: 110450.
38. Zhu X, Wang X, Wang Y, Zhao Y. The regulatory network among CircHIPK3, LncGAS5, and miR-495 promotes Th2 differentiation in allergic rhinitis. Cell Death Dis 2020; 11: 216.
39. Jia J, Xiang X, Yuan Y, He Y, Li D. METTL 3 in bronchial epithelial cells regulates the immune equilibrium of Th1_Th2 cells. Am J Respir Crit Care 2020; 201: A3055.
40. Ni X, Li X, Hu B, Wang L. Chronic allergic asthma alters m6A epitranscriptomic tagging of mRNAs and lncRNAs in the lung. Biosci Rep 2022; 42: BSR20221395.
41. Grossman J. One airway, one disease. Chest 1997; 111: 11s-6s.
42. Patil DP, Chen CK, Pickering BF, et al. m(6)A RNA methylation promotes XIST-mediated transcriptional repression. Nature 2016; 537: 369-73.
43. Zhang Y, Zhang W, Zhao J, et al. m(6)A RNA modification regulates innate lymphoid cell responses in a lineage-specific manner. Nat Immunol 2023; 24: 1256-64.
44. Peng YJ, Sun JH, Wang HS, Chen L, Sheng CR. Clinical observation on the treatment of allergic rhinitis by Xuanfei Tongqiao. Xian Dai Zhong Xi Yi Jie He Za Zhi 2016; 25: 3024-6.
45. Cui J, Dong M, Yi L, et al. Acupuncture inhibited airway inflammation and group 2 innate lymphoid cells in the lung in an ovalbumin-induced murine asthma model. Acupunct Med 2021; 39: 217-25.
46. Zeng CL, Lyu HQ, Peng YJ. Clinical efficacy of Xuanfei Tongqiao acupuncture in treatment of allergic rhinitis based on real world. Zhong Guo Zhong Yi Yao Xin Xi Za Zhi 2024; 31: 141-9.
47. Xie H. Clinical observation of Xuanfei Tongqiao acupuncture therapy combined with self-blood acupoint injection in the treatment of allergic rhinitis and its impact on intestinal microflora. Nanjing: Nanjing University of Chinese Medicine, 2021: 22.
48. Zhu X, Wang X, Wang Y, Zhao Y. Exosomal long non-coding RNA GAS5 suppresses Th1 differentiation and promotes Th2 differentiation via downregulating EZH2 and T-bet in allergic rhinitis. Mol Immunol 2020; 118: 30-9.
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