Therapeutic effects of acupuncture in rheumatoid arthritis are associated with centromere protein F expression

Main Article Content

Weitao Dong
Bin Wang
Rongchao Zhang
Junyi Cao
Rong Wu

Keywords

rheumatoid arthritis, CENPF, acupuncture, collagen-induced arthritis

Abstract

Rheumatoid arthritis is a globally common autoimmune inflammatory disease found especially in China. Acupuncture (AP), a traditional Chinese medicine (TCM) treatment method, is commonly used for treating rheumatoid arthritis. Many studies have demonstrated that acupuncture alone or in combination with other treatments is beneficial to treat clinical situation of rheumatoid arthritis, thus improving function and quality of life. In this study, we found that centromere protein F (CENPF) is a key gene in rheumatoid arthritis with acupuncture treatment by using differentially expressed genes (DEGs) and random forest model analysis of GSE57983 and GSE77298. Acupuncture helps to up-regulate the expression of CENPF in tissues in rheumatoid arthritis. Functionally, overexpression of CENPF inhibits monocyte chemoattractant protein (MCP)-1, tumor necrosis factor (TNF)-α, and Interleukin (IL)-6 expressions whereas deficiency of CENPF facilitates MCP-1, TNF-α, and IL-6 expressions in a collagen-induced arthritis (CIA) rat model. Furthermore, knocked down CENPF with acupuncture treatment antagonizes the inhibition of MCP-1, TNF-α, and IL-6 expressions in a CIA rat model. CENPF could be a crucial biomarker in regulating function of acupuncture in treating rheumatoid arthritis.


Objective: The objective of this study is to study the critical role of CENPF in regulation of rheumatoid arthritis with acupuncture treatment.


Methods: PCA was used to analyze the different expression genes between AP treatment group and control group. Volcano plot and random forest model were used to analyze the decreased and increased expression genes. RT-qPCR and IF were used to measure the expression of CENPF in CIA model rat with or without AP treatment. The expression of MCP-1, TNF-α and IL-6 was measured by western blotting. The pathology character and arthritis index were used to analyze the severity of joint injury.


Results: PCA data showed that the expression of genes was different between AP treatment group and control group from GEO datasets. Volcano plot and random forest model analysis indicated that CENPF is the most significantly increased expression gene after AP treatment. RT-qPCR and IF assay showed that CENPF is reduced expression in CIA model rat, while CENPF is upregulated expression in CIA model rat with AP treatment. Furthermore, overexpression of CENPF reduced the increasing of MCP-1, TNF-α and IL-6 in CIA model rat. On the contrary, CENPF deficiency induced the expression of MCP-1, TNF-α and IL-6 in CIA model rat. Additionally, the expression of MCP-1, TNF-α and IL-6 in CIA model rat was suppressed, whereas knockdown of CENPF antagonized the decrease of MCP-1, TNF-α and IL-6 in CIA model rat with AP treatment.


Conclusions: CENPF may be a key gene in regulation of the therapeutic effects of acupuncture in rheumatoid arthritis.

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References

1. Smolen JS, Aletaha D, McInnes IB. Rheumatoid arthritis. Lancet. 2016;388(10055):2023–38. 10.1016/S0140-6736(16)30173-8

2. Singh JA, Saag KG, Bridges SLJr., Akl EA, Bannuru RR, Sullivan MC, et al. 2015 American College of Rheumatology Guideline for the treatment of rheumatoid arthritis. Arthritis Rheumatol. 2016;68(1):1–26. 10.1002/art.39480

3. Mazaud C, Fardet L. Relative risk of and determinants for adverse events of methotrexate prescribed at a low dose: A systematic review and meta-analysis of randomized placebo-controlled trials. Br J Dermatol. 2017;177(4):978–86. 10.1111/bjd.15377

4. Xu Y, Hong S, Zhao X, Wang S, Xu Z, Ding S, et al. Acupuncture alleviates rheumatoid arthritis by immune-network modulation. Am J Chin Med. 2018;46(5):997–1019. 10.1142/S0192415X18500520

5. Barnes PM, Bloom B, Nahin RL. Complementary and alternative medicine use among adults and children: United States, 2007. Natl Health Stat Report. 2008 Dec 10;(12):1–23. 10.1037/e623942009-001. PMid: 19361005

6. Seo SY, Lee KB, Shin JS, Lee J, Kim MR, Ha IH, et al. Effectiveness of acupuncture and electroacupuncture for chronic neck pain: A systematic review and meta-analysis. Am J Chin Med. 2017;45(8):1573–95. 10.1142/S0192415X17500859

7. Torres-Rosas R, Yehia G, Pena G, Mishra P, del Rocio Thompson-Bonilla M, Moreno-Eutimio MA, et al. Dopamine mediates vagal modulation of the immune system by electroacupuncture. Nature Med. 2014;20(3):291–5. 10.1038/nm.3479

8. Bernateck M, Becker M, Schwake C, Hoy L, Passie T, Parlesak A, et al. Adjuvant auricular electroacupuncture and autogenic training in rheumatoid arthritis: A randomized controlled trial. Auricular acupuncture and autogenic training in rheumatoid arthritis. Forsch Komplementmed. 2008;15(4):187–93. 10.1159/000141929

9. Ouyang BS, Gao J, Che JL, Zhang Y, Li J, Yang HZ, et al. Effect of electro-acupuncture on tumor necrosis factor-alpha and vascular endothelial growth factor in peripheral blood and joint synovia of patients with rheumatoid arthritis. Chin J Integr Med. 2011;17(7):505–9. 10.1007/s11655-011-0783-2

10. Hur K, Jearn LH, Kim TY. Centromere protein-F-like pattern in a patient with rheumatoid arthritis. Ann Lab Med. 2019;39(2):227–8. 10.3343/alm.2019.39.2.227

11. Lourido L, Ruiz-Romero C, Picchi F, Diz-Rosales N, Vilaboa-Galan S, Fernandez-Lopez C, et al. Association of serum anti-centromere protein F antibodies with clinical response to infliximab in patients with rheumatoid arthritis: A prospective study. Semin Arthritis Rheum. 2020;50(5):1101–8. 10.1016/j.semarthrit.2020.06.010

12. Pennathur A, Xi L, Litle VR, Gooding WE, Krasinskas A, Landreneau RJ, et al. Gene expression profiles in esophageal adenocarcinoma predict survival after resection. J Thorac Cardiovasc Surg. 2013;145(2):505–12; discussion 12–3. 10.1016/j.jtcvs.2012.10.031

13. Dong L, Yu L, Bai C, Liu L, Long H, Shi L, et al. USP27-mediated cyclin E stabilization drives cell cycle progression and hepatocellular tumorigenesis. Oncogene. 2018;37(20):2702–13. 10.1038/s41388-018-0137-z

14. Yu L, Dong L, Wang Y, Liu L, Long H, Li H, et al. Reversible regulation of SATB1 ubiquitination by USP47 and SMURF2 mediates colon cancer cell proliferation and tumor progression. Cancer Lett. 2019;448:40–51. 10.1016/j.canlet.2019.01.039

15. Yu L, Dong L, Li H, Liu Z, Luo Z, Duan G, et al. Ubiquitination-mediated degradation of SIRT1 by SMURF2 suppresses CRC cell proliferation and tumorigenesis. Oncogene. 2020;39(22):4450–64. 10.1038/s41388-020-1298-0

16. Ramos A, Dominguez J, Gutierrez S. Acupuncture for rheumatoid arthritis. Medwave. 2018;18(6):e7284. 10.5867/medwave.2018.06.7283

17. Wu MY, Huang MC, Liao HH, Chiang JH, Lee YC, Hsu CY, et al. Acupuncture decreased the risk of coronary heart disease in patients with rheumatoid arthritis in Taiwan: A Nationwide propensity score-matched study. BMC Complement Altern Med. 2018;18(1):341. 10.1186/s12906-018-2384-5

18. Liu J, Huang Z, Zhang GH. Involvement of NF-kappaB signal pathway in acupuncture treatment of patients with rheumatoid arthritis. Zhen ci Yan Jiu = Acupunct Res. 2020;45(11):914–9.

19. Zhou CJ, Wang XY, Han Z, Wang DH, Ma YZ, Liang CG. Loss of CENPF leads to developmental failure in mouse embryos. Cell Cycle. 2019;18(20):2784–99. 10.1080/15384101.2019.1661173

20. Chen EB, Qin X, Peng K, Li Q, Tang C, Wei YC, et al. HnRNPR-CCNB1/CENPF axis contributes to gastric cancer proliferation and metastasis. Aging. 2019;11(18):7473–91. 10.18632/aging.102254

21. Lin SC, Kao CY, Lee HJ, Creighton CJ, Ittmann MM, Tsai SJ, et al. Dysregulation of miRNAs-COUP-TFII-FOXM1-CENPF axis contributes to the metastasis of prostate cancer. Nat Commun. 2016;7:11418. 10.1038/ncomms11418

22. Kullmann F, Judex M, Ballhorn W, Justen HP, Wessinghage D, Welsh J, et al. Kinesin-like protein CENP-E is upregulated in rheumatoid synovial fibroblasts. Arthritis Res. 1999;1(1):71–80. 10.1186/ar13

23. Watanabe M, Kainuma E, Tomiyama C. Repetitive manual acupuncture increases markers of innate immunity in mice subjected to restraint stress. Acupunct Med. 2015;33(4):312–8. 10.1136/acupmed-2014-010660

24. Yang F, Gong Y, Yu N, Yao L, Zhao X, Hong S, et al. ST36 Acupuncture alleviates the inflammation of adjuvant-induced arthritic rats by targeting monocyte/macrophage modulation. Evidence Complemen Alternat Med eCAM. 2021;2021:9430501. 10.1155/2021/9430501