Wnt信号通路在自身免疫性疾病中的作用研究进展
Research Progress on the Role of Wnt Signaling Pathway in Autoimmune Diseases
摘要: Wnt信号通路的异常激活与许多人类疾病的发病机制有关，越来越多的研究表明，Wnt信号通路的异常调控在多发性硬化症、类风湿关节炎、系统性红斑狼疮、原发性干燥综合征等自身免疫性疾病(AID)的发病机制中发挥着关键作用。该文综述了自身免疫性疾病中Wnt通路相关的最新研究进展，展现了近年来对Wnt信号通路在自身免疫性疾病中的致病作用的认识，以期能更加全面地了解Wnt信号通路与自身免疫性疾病发生发展的关系，旨在为自身免疫性疾病的治疗提供新思路。
Abstract: The abnormal activation of Wnt signaling pathway is related to the pathogenesis of many human diseases. More and more studies show that the abnormal regulation of Wnt signal pathway plays a key role in the pathogenesis of autoimmune diseases (AID), such as multiple sclerosis, rheumatoid arthritis, systemic lupus erythematosus, primary Sjogren’s syndrome, and so on. This paper reviews the latest research progress related to Wnt pathway in autoimmune diseases, and shows the un-derstanding of the pathogenic role of Wnt signaling pathway in autoimmune diseases in recent years, in order to more comprehensively understand the relationship between Wnt signaling pathway and the occurrence and development of autoimmune diseases, so as to provide new ideas for the treatment of autoimmune diseases.
文章引用：徐小凡, 李一鸣, 徐小虎, 代义龙, 金呈强. Wnt信号通路在自身免疫性疾病中的作用研究进展[J]. 医学诊断, 2023, 13(4): 432-439. https://doi.org/10.12677/MD.2023.134066

参考文献

[1] Conrad, K., Shoenfeld, Y. and Fritzler, M.J. (2020) Precision Health: A Pragmatic Approach to Understanding and Addressing Key Factors in Autoimmune Diseases. Autoimmunity Reviews, 19, Article ID: 102508.
https://doi.org/10.1016/j.autrev.2020.102508
[2] Cooper, G.S., Bynum, M.L. and Somers, E.C. (2009) Recent Insights in the Epidemiology of Autoimmune Diseases: Improved Prevalence Estimates and Understanding of Clustering of Diseases. Journal of Au-toimmunity, 33, 197-207.
https://doi.org/10.1016/j.jaut.2009.09.008
[3] Shi, J., Chi, S., Xue, J., Yang, J., Li, F. and Liu, X. (2016) Emerging Role and Therapeutic Implication of Wnt Signaling Pathways in Autoimmune Diseases. Journal of Immunology Research, 2016, Article ID: 9392132.
https://doi.org/10.1155/2016/9392132
[4] 龚晓红, 李桓, 陆超群, 等. 基于Notch与Wnt/β-Catenin通路探讨黄芪甲苷对人成纤维细胞间质转化的作用[J/OL]. 中华中医药学刊, 2023: 1-20.
http://kns.cnki.net/kcms/detail/21.1546.R.20230828.1435.008.html
[5] Zhu, H., Zou, X., Lin, S., Hu, X. and Gao, J. (2020) Effects of Naringin on Reversing Cisplatin Resistance and the Wnt/Beta-Catenin Pathway in Human Ovarian Cancer SKOV3/CDDP Cells. Journal of International Medical Research, 48, 1-9.
https://doi.org/10.1177/0300060519887869
[6] 施佳蕾, 乔丹丹, 何倩, 何慧芬, 秦爱建, 钱琨. Wnt信号通路在疾病中的调控作用研究进展[J]. 中国动物传染病学报, 2021, 29(4): 31-43.
[7] Nusse, R. and Clevers, H. (2017) Wnt/Beta-Catenin Signaling, Disease, and Emerging Therapeutic Modalities. Cell, 169, 985-999.
https://doi.org/10.1016/j.cell.2017.05.016
[8] 王佳, 刘毅, 赵毅. Wnt信号途径与自身免疫疾病发生发展的关系研究进展[J]. 实用医院临床杂志, 2014, 11(3): 146-148.
[9] Katoh, M. (2005) WNT/PCP Signaling Pathway and Human Cancer (Review). Oncology Reports, 14, 1583-1588.
https://doi.org/10.3892/or.14.6.1583
[10] Kühl, M., Sheldahl, L.C., Malbon, C.C. and Moon, R.T. (2000) Ca2+/Calmodulin-Dependent Protein Kinase II Is Stimulated by Wnt and Frizzled Homologs and Promotes Ventral Cell Fates in Xenopus. Journal of Biological Chemistry, 275, 12701-12711.
https://doi.org/10.1074/jbc.275.17.12701
[11] Galluzzi, L., Spranger, S., Fuchs, E. and Lopez-Soto, A. (2019) WNT Signaling in Cancer Immunosurveillance. Trends in Cell Biology, 29, 44-65.
https://doi.org/10.1016/j.tcb.2018.08.005
[12] Liu, D., Zhao, H., Zhao, S. and Wang, X. (2014) MicroRNA Expression Profiles of Peripheral Blood Mononuclear Cells in Patients with Systemic Lupus Erythematosus. Acta Histochemica, 116, 891-897.
https://doi.org/10.1016/j.acthis.2014.02.009
[13] Deng, Y.J., Huang, Z.X., Zhou, C.J., Wang, J.W., You, Y., Song, Z.Q., et al. (2006) Gene Profiling Involved in Immature CD4+ T Lymphocyte Responsible for Systemic Lupus Erythematosus. Molecular Immu-nology, 43, 1497-1507.
https://doi.org/10.1016/j.molimm.2005.07.039
[14] Long, L., Liu, Y., Wang, S., Zhao, Y., Guo, J., Yu, P., et al. (2010) Dick-kopf-1 as Potential Biomarker to Evaluate Bone Erosion in Systemic Lupus Erythematosus. Journal of Clinical Immunology, 30, 669-675.
https://doi.org/10.1007/s10875-010-9436-z
[15] Tan, Y., Song, D., Wu, L.H., Yu, F. and Zhao, M.H. (2013) Serum Levels and Renal Deposition of C1q Complement Component and Its Antibodies Reflect Disease Activity of Lupus Nephritis. BMC Nephrology, 14, Article No. 63.
https://doi.org/10.1186/1471-2369-14-63
[16] Lu, C., Shao, X., Zhou, S. and Pan, C. (2021) LINC00176 Facilitates CD4+ T Cell Adhesion in Systemic Lupus Erythematosus via the WNT5a Signaling Pathway by Regulating WIF1. Molecular Immunology, 134, 202-209.
https://doi.org/10.1016/j.molimm.2021.02.018
[17] Maclauchlan, S., Zuriaga, M.A., Fuster, J.J., Cuda, C.M., Jonason, J., Behza-di, F., et al. (2017) Genetic Deficiency of Wnt5a Diminishes Disease Severity in a Murine Model of Rheumatoid Arthritis. Arthritis Research & Therapy, 19, Article No. 166.
https://doi.org/10.1186/s13075-017-1375-0
[18] Guo, G., Wang, H., Ye, L., Shi, X., Yan, K., Lin, K., et al. (2019) Hsa_circ_0000479 as a Novel Diagnostic Biomarker of Systemic Lupus Erythematosus. Frontiers in Immunology, 10, Article 2281.
https://doi.org/10.3389/fimmu.2019.02281
[19] Gu, Z., Tan, W., Feng, G., Meng, Y., Shen, B., Liu, H., et al. (2014) Wnt/Beta-Catenin Signaling Mediates the Senescence of Bone Marrow-Mesenchymal Stem Cells from Systemic Lupus Erythematosus Patients through the p53/p21 Pathway. Molecular and Cellular Biochemistry, 387, 27-37.
https://doi.org/10.1007/s11010-013-1866-5
[20] Bartok, B. and Firestein, G.S. (2010) Fibroblast-Like Synoviocytes: Key Effec-tor Cells in Rheumatoid Arthritis. Immunological Reviews, 233, 233-255.
https://doi.org/10.1111/j.0105-2896.2009.00859.x
[21] Fassio, A., Adami, G., Giollo, A., Viapiana, O., Malavolta, N., Saviola, G., et al. (2020) Acute Effects of Glucocorticoid Treatment, TNFalpha or IL-6R Blockade on Bone Turnover Markers and Wnt Inhibi-tors in Early Rheumatoid Arthritis: A Pilot Study. Calcified Tissue International, 106, 371-377.
https://doi.org/10.1007/s00223-019-00649-3
[22] Cici, D., Corrado, A., Rotondo, C. and Cantatore, F.P. (2019) Wnt Signaling and Biological Therapy in Rheumatoid Arthritis and Spondyloarthritis. International Journal of Molecular Sciences, 20, Article 5552.
https://doi.org/10.3390/ijms20225552
[23] Liu, Y.Y., Wang, S.Y., Li, Y.N., Bian, W.J., Zhang, L.Q., Li, Y.H., et al. (2020) Activity of Fibroblast-Like Synoviocytes in Rheumatoid Arthritis Was Impaired by Dickkopf-1 Targeting siRNA. Chinese Medical Journal (England), 133, 679-686.
https://doi.org/10.1097/CM9.0000000000000697
[24] Malysheva, K., de Rooij, K., Lowik, C.W., Baeten, D.L., Rose-John, S., Stoika, R., et al. (2016) Interleukin 6/Wnt Interactions in Rheumatoid Arthritis: Interleukin 6 Inhibits Wnt Signaling in Synovial Fibro-blasts and Osteoblasts. Croatian Medical Journal, 57, 89-98.
https://doi.org/10.3325/cmj.2016.57.89
[25] Cheon, H., Boyle, D.L. and Firestein, G.S. (2004) Wnt1 Inducible Signaling Pathway Protein-3 Regulation and Microsatellite Structure in Arthritis. The Jour-nal of Rheumatology, 31, 2106-2114.
[26] Nakamura, Y., Nawata, M. and Wakitani, S. (2005) Expression Profiles and Functional Analyses of Wnt-Related Genes in Human Joint Disorders. The American Journal of Pathology, 167, 97-105.
https://doi.org/10.1016/S0002-9440(10)62957-4
[27] Cai, L., Mu, Y.R., Liu, M.M., Zhou, M.Y., Meng, B., Liu, F.Y., et al. (2021) Penta-Acetyl Geniposide Suppresses Migration, Invasion, and Inflammation of TNF-alpha-Stimulated Rheumatoid Arthritis Fibroblast-Like Synoviocytes Involving Wnt/Beta-Catenin Signaling Pathway. Inflammation, 44, 2232-2245.
https://doi.org/10.1007/s10753-021-01495-y
[28] Jiang, P., Wei, K., Chang, C., Zhao, J., Zhang, R., Xu, L., et al. (2022) SFRP1 Negatively Modulates Pyroptosis of Fibroblast-Like Synoviocytesin Rheumatoid Arthritis: A Review. Frontiers in Immunology, 13, Article 903475.
https://doi.org/10.3389/fimmu.2022.903475
[29] Ullman, T.A. and Itzkowitz, S.H. (2011) Intestinal Inflammation and Cancer. Gastroenterology, 140, 1807-1816.
https://doi.org/10.1053/j.gastro.2011.01.057
[30] Terry, R., Chintanaboina, J., Patel, D., Lippert, B., Haner, M., Price, K., et al. (2019) Expression of WIF-1 in Inflammatory Bowel Disease. Histology and Histopathology, 34, 149-157.
[31] Tian, Y., Xu, J., Li, Y., Zhao, R., Du, S., Lv, C., et al. (2019) MicroRNA-31 Reduces Inflammatory Signaling and Promotes Regeneration in Colon Epithelium, and Delivery of Mimics in Microspheres Reduces Colitis in Mice. Gastroenterology, 156, 2281-2296.
https://doi.org/10.1053/j.gastro.2019.02.023
[32] Armbruster, N.S., Stange, E.F. and Wehkamp, J. (2017) In the Wnt of Paneth Cells: Immune-Epithelial Crosstalk in Small Intestinal Crohn’s Disease. Frontiers in Immunology, 8, Article 1204.
https://doi.org/10.3389/fimmu.2017.01204
[33] Bai, W., Bai, J., Li, Y., Tian, D. and Shi, R. (2017) Microtubule-Associated Pro-tein 1S-Related Autophagy Inhibits Apoptosis of Intestinal Epithelial Cells via Wnt/Beta-Catenin Signaling in Crohn’s Disease. Bio-chemical and Biophysical Research Communications, 485, 635-642.
https://doi.org/10.1016/j.bbrc.2017.02.034
[34] Henderson, J., Brown, M., Horsburgh, S., Duffy, L., Wilkinson, S., Worrell, J., et al. (2019) Methyl Cap Binding Protein 2: A Key Epigenetic Protein in Systemic Sclerosis. Rheumatology (Oxford), 58, 527-535.
https://doi.org/10.1093/rheumatology/key327
[35] Long, Y., Chen, W., Du, Q., Zuo, X. and Zhu, H. (2018) Ubiquitination in Scleroderma Fibrosis and Its Treatment. Frontiers in Immunology, 9, Article 2383.
https://doi.org/10.3389/fimmu.2018.02383
[36] 杨晓静, 孟玮, 徐宏俊, 周向昭. 长链非编码BANCR通过激活Wnt/β-Catenin信号通路调控黑色素瘤细胞迁移和侵袭行为[J]. 中国免疫学杂志, 2018, 34(1): 50-54+59.
[37] Wang, W., Walker, J.R., Wang, X., Tremblay, M.S., Lee, J.W., Wu, X., et al. (2009) Identification of Small-Molecule Inducers of Pancreatic Beta-Cell Expansion. Proceedings of the National Academy of Sciences of the United States of America, 106, 1427-1432.
https://doi.org/10.1073/pnas.0811848106
[38] He, X., Han, W., Hu, S.X., Zhang, M.Z., Hua, J.L. and Peng, S. (2015) Canonical Wnt Signaling Pathway Contributes to the Proliferation and Survival in Porcine Pancre-atic Stem Cells (PSCs). Cell and Tissue Research, 362, 379-388.
https://doi.org/10.1007/s00441-015-2220-x
[39] Karatas, A., Omercikoglu, Z., Oz, B., Dagli, A.F., Catak, O., Erman, F., et al. (2021) Wnt Signaling Pathway Activities May Be Altered in Primary Sjogren’s Syndrome. Turkish Journal of Medical Sciences, 51, 2015-2022.
https://doi.org/10.3906/sag-2102-367
[40] Czepiel, M., Diviani, D., Jazwa-Kusior, A., Tkacz, K., Rolski, F., Smolenski, R.T., et al. (2022) Angiotensin II Receptor 1 Controls Profibrotic Wnt/Beta-Catenin Signalling in Experimental Autoimmune Myocarditis. Car-diovascular Research, 118, 573-584.
https://doi.org/10.1093/cvr/cvab039
[41] Zhang, Z., Li, Y., Chen, N., Li, H., Chen, S., Cui, X., et al. (2023) Pertussis Toxin-Induced Inhibition of Wnt/Beta-Catenin Signaling in Dendritic Cells Promotes an Autoimmune Re-sponse in Experimental Autoimmune Uveitis. Journal of Neuroinflammation, 20, Article No. 24.
https://doi.org/10.1186/s12974-023-02707-y