Notch信号通路活化在COPD中的作用
The Role of Notch Signaling Pathway in COPD
DOI: 10.12677/ACM.2020.108235, PDF,    国家社会科学基金支持
作者: 吴婉柳：河南中医药大学河南省呼吸道疾病中医重点实验室，河南 郑州；长江大学医学部中医系，湖北 荆州；钱 锋：长江大学医学部生理系，湖北 荆州；黄江荣*：长江大学医学部中医系，湖北 荆州
关键词: 慢性阻塞性肺气肿；COPD；Notch信号通路；Chronic Obstructive Emphysema； COPD； Notch Signaling Pathway
摘要: 慢性阻塞性肺疾病(Chronic obstructive pulmonary disease, COPD)是一种持续存在的气流受限，呈进行性发展，伴有气道和肺慢性炎症反应的常见疾病。Notch是一种跨膜蛋白，通过直接的细胞–细胞间接触调节慢性阻塞性肺疾病、肺动脉高压和肺癌的病理生理功能过程。本文就Notch信号与COPD的关系对近来的研究进行综述，重点讨论了Notch信号通路活化参与免疫炎症紊乱、气道上皮–间质转化、肺间质纤维化，促进Klotho甲基化加重肺损伤等可能的COPD新病理机制，为临床治疗COPD提供新思路。
Abstract: Chronic obstructive pulmonary disease (COPD) is a common disease that is characterized by the progressive, persistent restriction in airflow and chronic inflammation of the respiratory tract and lungs. Notch is a transmembrane protein that regulates the pathophysiological processes of COPD, pulmonary hypertension, and lung cancer through direct cell-cell contact. This mini-review focuses on the illustration of the relationship between the Notch signaling and COPD in terms of the involvement of Notch signaling pathway in immune inflammatory disorders, airway epithelial-interstitial transformation, pulmonary fibrosis and the promotion of Klotho methylation aggravating lung injury, which provides new insights into the pathological mechanisms and clinical treatment of COPD.
文章引用：吴婉柳, 钱锋, 黄江荣. Notch信号通路活化在COPD中的作用[J]. 临床医学进展, 2020, 10(8): 1573-1580. https://doi.org/10.12677/ACM.2020.108235

参考文献

[1] Wang, C., Xu, J.Y., Yang, L., et al. (2018) Prevalence and Risk Factors of Chronic Obstructive Pulmonary Disease in China (the China Pulmonary Health [CPH] Study): A National Cross-Sectional Study. The Lancet, 391, 1706-1717. [Google Scholar] [CrossRef] 
[2] Celli, B.R. and Wedzicha, J.A. (2019) Update on Clinical Aspects of COPD Reply. The New England Journal of Medicine, 381, 2485-2486. [Google Scholar] [CrossRef] 
[3] GBD 2017 Causes of Death Collaborators (2018) Global, Regional, and National Age-Sex-Specific Mortality for 282 Causes of Death in 195 Countries and Territories, 1980-2017: A Systematic Analysis for the Global Burden of Disease Study 2017. The Lancet, 392, 1736-1788.
[4] Mirza, S., Clay, R.D. and Koslow, M.A. (2018) COPD Guidelines: A Review of the 2018 GOLD Report. Mayo Clinic Proceedings, 93, 1488-1502. [Google Scholar] [CrossRef] [PubMed]
[5] Kiyokawa, H. and Morimoto, M. (2020) Notch Signaling in the Mammalian Respiratory System, Specifically the Trachea and Lungs, in Development, Homeostasis, Regeneration, and Disease. Development, Growth & Differentiation, 62, 67-79. [Google Scholar] [CrossRef] [PubMed]
[6] Guruharsha, K.G., Kankel, M.W., Artavanis-Tsakonas, S., et al. (2012) The Notch Signalling System: Recent Insights into the Complexity of a Conserved Pathway. Nature Reviews Genetics, 13, 654-666. [Google Scholar] [CrossRef] [PubMed]
[7] Siebel, C. and Lendahl, U. (2017) Notch Signaling in Development, Tissue Homeostasis, and Disease. Physiological Reviews, 97, 1235-1294. [Google Scholar] [CrossRef] [PubMed]
[8] Bray, S. (1998) Notch Signalling in Drosophilia: Three Ways to Use a Pathway. Seminars in Cell and Developmental Biology, 9, 591-597. [Google Scholar] [CrossRef] [PubMed]
[9] Jing, Y., Gimenes, J.A. and Mishra, R. (2019) Notch3 Contributes to Rhinovirus-Induced Goblet Cell Hyperplasia in COPD Airway Epithelial Cells. Thorax, 74, 18-32. [Google Scholar] [CrossRef] [PubMed]
[10] Boucherat, O., Chakir, J. and Jeannotte, L. (2012) The Loss of Hoxa5 Function Promotes Notch-Dependent Goblet Cell Metaplasia in Lung Airways. Biology Open, 1, 677-691. [Google Scholar] [CrossRef] [PubMed]
[11] Xing, Y., Li, A., Borok, Z., et al. (2012) NOTCH1 Is Required for Regeneration of Clara Cells during Repair of Airway Injury. Stem Cells, 30, 946-955. [Google Scholar] [CrossRef] [PubMed]
[12] Jiang, J., Xiao, K. and Chen, P. (2017) Notch Signaling in Lung Diseases. Experimental Lung Research, 43, 217-228. [Google Scholar] [CrossRef] [PubMed]
[13] Agustí, A. and Hogg, J.C. (2019) Update on the Pathogenesis of Chronic Obstructive Pulmonary Disease. The New England Journal of Medicine, 381, 1248-1256. [Google Scholar] [CrossRef] 
[14] 王颖莹, 潘涛, 贾凡, 等. 人外周血初始CD4+T细胞向Th17细胞分化条件研究[J]. 检验医学与临床, 2017, 14(7): 948-950.
[15] 张晓军, 何韶衡. 老年COPD患者痰IL-18、-16、-4及IFN-γ水平的相关性研究及临床意义[J]. 实用医学杂志, 2005, 21(11): 1145-1147.
[16] 杨晶, 邝相如. CD4+T细胞亚群失衡在慢性阻塞性肺疾病中的临床意义[J]. 中国现代医学杂志, 2015, 25(1): 46-49.
[17] 李志芳, 张倩, 吴世满. 慢性阻塞性肺疾病患者外周血Th17、CD4+Treg细胞的检测及意义[J]. 国际呼吸杂志, 2014(1): 31-35.
[18] 周鹏, 梁爱武, 张惠敏, 等. 白介素-17在慢性阻塞性肺疾病中的表达变化研究概况[J]. 中国民族民间医药, 2016, 25(12): 55-57.
[19] 刘迪, 牛逸群, 疏欣杨, 等. 百令胶囊对慢性阻塞性肺疾病稳定期患者免疫、炎症及氧化应激指标的影响[J]. 世界中西医结合杂志, 2020, 15(3): 425-433.
[20] 张占强, 吴春艳, 方彬, 等. Th17/Treg、IL-17在慢性阻塞性肺疾病患者中的表达及与肺功能的相关性[J]. 现代中西医结合杂志, 2018, 27(22): 2419-2423.
[21] 郝小梅, 彭文照, 刘梅. 不同分期慢性阻塞性肺病患者T淋巴细胞亚群细胞因子变化及其与肺功能的相关性研究[J]. 广州医科大学报, 2018, 46(1): 7-10.
[22] Diller, M.L., Kudchadkar, R.R., Delman, K.A., et al. (2016) Balancing Inflammation: The Link between Th17 and Regulatory T Cells. Mediators of Inflammation, 10, 219-226. [Google Scholar] [CrossRef] [PubMed]
[23] Duffy, S.P. (2019) Chronic Obstructive Pulmonary Disease: Evaluation and Management. Medical Clinics of North America, 103, 453-461. [Google Scholar] [CrossRef] [PubMed]
[24] 谢东杰, 王爱迪, 吴晶魁, 等. Notch信号通路对CD4+T细胞分化及功能调控的研究进展[J]. 免疫学杂志, 2017, 33(12): 1100-1104.
[25] Yang, X.N., Liu, X.J., Zhao, L.T., et al. (2016) Effects and Mechanisms of Notch Signaling Pathway on Immune Imbalance in Chronic Obstructive Pulmonary Disease. Chinese Journal of Tuberculosis and Respiratory Diseases, 39, 881-885.
[26] Gu, X.Y., Chu, X., Zeng, X.L., et al. (2017) Effects of PM2.5 Exposure on the Notch Signaling Pathway and Immune Imbalance in Chronic Obstructive Pulmonary Disease. Environmental Pollution, 226, 163-173. [Google Scholar] [CrossRef] [PubMed]
[27] D’Souza, B., Meloty-Kapella, L. and Weinmaster, G. (2010) Chapter Three-Canonical and Non-Canonical Notch Ligands. Current Topics in Developmental Biology, 92, 73-129. [Google Scholar] [CrossRef] 
[28] Ballester-López, C., Conlon, T.M., Ertüz, Z., et al. (2019) The Notch Ligand DNER Regulates Macrophage IFNγ Release in Chronic Obstructive Pulmonary Disease. EBioMedicine, 43, 562-575. [Google Scholar] [CrossRef] [PubMed]
[29] 吴海兰, 辛晓峰. 上皮间充质转化与慢性阻塞性肺疾病的气道重塑[J]. 医学研究生学报, 2015, 28(9): 1004-1008.
[30] Godinas, L., Corhay, J.L., Henket, M., et al. (2017) Increased Production of TGF-β1 from Sputum Cells of COPD: Relationship with Airway Obstruction. Cytokine, 99, 1-8. [Google Scholar] [CrossRef] [PubMed]
[31] Li, S., Hu, X., Wang, Z., et al. (2015) Different Profiles of Notch Signaling in Cigarette Smoke-Induced Pulmonary Emphysema and Bleomycin-Induced Pulmonary Fibrosis. Inflammation Research, 64, 363-371. [Google Scholar] [CrossRef] [PubMed]
[32] Hussain, M., Xu, C., Ahmad, M., et al. (2017) Notch Signaling: Linking Embryonic Lung Development and Asthmatic Airway Remodeling. Molecular Pharmacology, 92, 676-693. [Google Scholar] [CrossRef] [PubMed]
[33] 33Tilley, A.E., Harvey, B.G., Heguy, et al. (2009) A Down-Regulation of the Notch Pathway in Human Airway Epithelium in Association with Smoking and Chronic Obstructive Pulmonary Disease. American Journal of Respiratory and Critical Care Medicine, 179, 457-466. [Google Scholar] [CrossRef] 
[34] 华华, 刘向国, 李杰. 补肾活血调营化痰方对慢性阻塞性肺疾病大鼠模型肺功能及转化生长因子-β1、炎性因子的影响[J]. 世界中西医结合杂志, 2019, 14(11): 1543-1546.
[35] Mahmood, M.Q., Reid, D., Ward, C., et al. (2017) Transforming Growth Factor (TGF) β1 and Smad Signalling Pathways: A Likely Key to EMT-Associated COPD Pathogenesis. Respirology, 22, 133-140. [Google Scholar] [CrossRef] [PubMed]
[36] 刘晨, 隋红. TGF-β信号通路介导胃癌EMT的研究进展[J]. 现代肿瘤医学, 2020, 28(3): 517-520.
[37] Matsuno, Y., Coelho, A.L., Jarai, G., Westwick, J. and Hogaboam, C.M. (2012) Notch Signaling Mediates TGF-β1-Induced Epithelial-Mesenchymal Transition through the Induction of Snai1. The International Journal of Biochemistry & Cell Biology, 44, 776-789. [Google Scholar] [CrossRef] [PubMed]
[38] 汤立建, 任敦强, 孙家兴, 等. Notch信号通路与肺纤维化关系的研究进展[J]. 青岛大学医学院学报, 2017, 53(5): 614-617.
[39] 魏胜全, 薛华, 王惠霞, 等. 罗红霉素联合N-乙酰半胱氨酸治疗慢性阻塞性肺疾病合并肺间质纤维化疗效及对患者肺功能的影响[J]. 陕西医学杂志, 2020, 49(5): 611-614.
[40] Vancheri, C., Gili, E., Failla, M., et al. (2005) Bradykinin Differentiates Human Lung Fibroblasts to a Myofibroblast Phenotype via the B2 Receptor. The Journal of Allergy and Clinical Immunology, 116, 1242-1248. [Google Scholar] [CrossRef] [PubMed]
[41] 符策富, 仕丽, 胡少丹, 等. NOTCH信号通路与肺纤维化发病机制的研究进展[J]. 现代养生, 2019, 4(8): 140-141.
[42] 徐芳, 刘红梅, 黄莺. 银杏叶提取物对特发性肺间质纤维化成纤维细胞表型转化过程中NOTCH信号通路的影响[J]. 中国中西医结合急救杂志, 2016(4): 417-420.
[43] Gustafsson, M.V., Zheng, X., Pereira, T., et al. (2005) Hypoxia Requires Notch Signaling to Maintain the Undifferentiated Cell State. Developmental Cell, 9, 617-628. [Google Scholar] [CrossRef] [PubMed]
[44] Kurosu, H., Yamamoto, M., Clark, J.D., et al. (2005) Suppression of Aging in Mice by the Hormone Klotho. Science, 309, 1829-1833. [Google Scholar] [CrossRef] [PubMed]
[45] Masuda, H., Chikuda, H., Suga, T., Kawaguchi, H. and KuroO, M. (2005) Regulation of Multiple Ageing-Like Phenotypes by Inducible Klotho Gene Expression in Klotho Mutant Mice. Mechanisms of Ageing and Development, 126, 1274-1283. [Google Scholar] [CrossRef] [PubMed]
[46] Li, L., Wang, Y., Gao, W., et al. (2015) Klotho Reduction in Alveolar Macrophages Contributes to Cigarette Smoke Extract-Induced Inflammation in Chronic Obstructive Pulmonary Disease. Journal of Biological Chemistry, 290, 27890-27900. [Google Scholar] [CrossRef] 
[47] Shen, N., Gong, T., Wang, J.D., et al. (2011) Cigarette Smoke Induced Pulmonary Inflammatory Responses Are Mediated by EGR-1/GGPPS/MAPK Signaling. The American Journal of Pathology, 178, 110-118. [Google Scholar] [CrossRef] [PubMed]
[48] Cui, W., Zhang, Z., Zhang, P., et al. (2018) Nrf2 Attenuates Inflammatory Response in COPD/Emphysema: Crosstalk with Wnt3a/b-Catenin and AMPK Pathways. Journal of Cellular and Molecular Medicine, 22, 3514-3525. [Google Scholar] [CrossRef] [PubMed]
[49] Qiu, J., Zhang, Y.N., Zheng, X., et al. (2018) Notch Promotes DNMT-Mediated Hypermethylation of Klotho Leads to COPD-Related Inflammation. Experimental Lung Research, 44, 368-377. [Google Scholar] [CrossRef] [PubMed]

为你推荐