哮喘患者气道上皮屏障功能受损的机制
Mechanism of Impaired Airway Epithelial Barrier Function in Patients with Asthma
DOI: 10.12677/ACM.2022.124470, PDF,   
作者: 吴 梦：重庆医科大学，重庆；李敏超*：重庆医科大学附属第二医院，重庆
关键词: 哮喘；气道上皮细胞；屏障功能；损伤机制；Asthma； Airway Epithelial Cells； Barrier Function； Damage Mechanism
摘要: 支气管哮喘是一类异质性疾病，发病机制主要与气道免疫–炎症、气道高反应性、气道重塑等相关。其中气道上皮屏障是呼吸道抵御外界有害物质的首要防线，发挥着化学、物理及免疫屏障的功能，是病理改变的主要部位之一。近年来已有许多研究发现哮喘患者的气道上皮屏障均受到不同程度的损害。气道上皮屏障的损伤与变应原、呼吸道感染、环境污染等因素息息相关，其中各种细胞因子、模式受体、信号通路参与其中。本篇综述主要介绍了气道上皮屏障的结构和分子组成，探讨上皮屏障功能障碍在哮喘发病机制中的作用以及简单介绍目前改善气道上皮屏障的一些治疗方法。
Abstract: Bronchial asthma is a heterogeneous disease, and its pathogenesis is mainly related to airway immune-inflammation, airway hyperresponsiveness and airway remodeling. Among them, airway epithelial barrier is the primary defense of respiratory tract against external harmful substances, plays the function of chemical, physical and immune barrier, and is one of the main parts of pathological changes. In recent years, many studies have found that the airway epithelial barrier in patients with asthma is damaged to varying degrees. The damage of airway epithelial barrier is closely related to allergen, respiratory tract infection and environmental pollution, among which various cytokines, model receptors and signaling pathways are involved. This review mainly in-troduces the structure and molecular composition of airway epithelial barrier, discusses the role of epithelial barrier dysfunction in the pathogenesis of asthma, and briefly introduces some current treatments for improving airway epithelial barrier.
文章引用：吴梦, 李敏超. 哮喘患者气道上皮屏障功能受损的机制[J]. 临床医学进展, 2022, 12(4): 3257-3264. https://doi.org/10.12677/ACM.2022.124470

参考文献

[1] Asthma Group of Chinese Throacic Society (2020) Guidelines for Bronchial Asthma Prevent and Management (2020 Edition). Chinese Journal of Tuberculosis and Respiratory Diseases, 43, 1023-1048.
[2] Soriano, J.B., et al. (2020) Prevalence and Attributable Health Burden of Chronic Respiratory Diseases, 1990-2017: A Systematic Analysis for the Global Burden of Disease Study 2017. The Lancet Respiratory Medicine, 8, 585-596.
[3] Viegi, G., Maio, S., Fasola, S. and Baldacci, S. (2020) Global Burden of Chronic Respiratory Diseases. Journal of Aerosol Medicine and Pulmonary Drug Delivery, 33, 171-177. [Google Scholar] [CrossRef] [PubMed]
[4] Huang, K., Yang, T., Xu, J., et al. (2019) Prevalence, Risk Factors, and Management of Asthma in China: A National Cross-Sectional Study. The Lancet, 394, 407-418. [Google Scholar] [CrossRef] 
[5] Fahy, J.V. (2015) Type 2 Inflammation in Asthma—Present in Most, Absent in Many. Nature Reviews Immunology, 15, 57-65. [Google Scholar] [CrossRef] [PubMed]
[6] Boonpiyathad, T., et al. (2019) Immunologic Mechanisms in Asthma. Sem-inars in Immunology, 46, Article ID: 101333. [Google Scholar] [CrossRef] [PubMed]
[7] Pain, M., Bermudez, O., Lacoste, P., et al. (2014) Tissue Re-modelling in Chronic Bronchial Diseases: From the Epithelial to Mesenchymal Phenotype. European Respiratory Review, 23, 118-130. [Google Scholar] [CrossRef] [PubMed]
[8] 游曼清, 王宋平. 气道上皮屏障在支气管哮喘防御机制中的研究进展[J]. 中华哮喘杂志(电子版), 2013, 7(5): 345-349.
[9] Manzanares, D., Gonzalez, C., Ivonnet, P., et al. (2011) Functional Apical Large Conductance, Ca2+-Activated, and Voltage-Dependent K+ Channels Are Required for Maintenance of Airway Surface Liquid Volume. Journal of Biological Chemistry, 286, 19830-19839. [Google Scholar] [CrossRef] 
[10] Nicolas, P. (2009) Multifunctional Host Defense Peptides: Intra-cellular-Targeting Antimicrobial Peptides. The FEBS Journal, 276, 6483-6496. [Google Scholar] [CrossRef] [PubMed]
[11] Kuperman, D.A., Huang, X., Koth, L.L., et al. (2002) Direct Effects of Interleukin-13 on Epithelial Cells Cause Airway Hyperreactivity and Mucus Overproduction in Asthma. Nature Medicine, 8, 885-889. [Google Scholar] [CrossRef] [PubMed]
[12] Evans, C., Kim, K., Tuvim, M.J. and Dickey, B.F. (2009) Mucus Hypersecretion in Asthma: Causes and Effects. Current Opinion in Pulmonary Medicine, 15, 4-11. [Google Scholar] [CrossRef] 
[13] Kirkham, S., Sheehan, J.K., Knight, D., Richardson, P.S. and Thornton, D.J. (2002) Heterogeneity of Airways Mucus: Variations in the Amounts and Glycoforms of the Major Oligomeric Mucins MUC5AC and MUC5B. Biochemical Journal, 361, 537-546. [Google Scholar] [CrossRef] 
[14] Zaragosi, L., Deprez, M. and Barbry, P. (2020) Using Single-Cell RNA Sequencing to Unravel Cell Lineage Relationships in the Respiratory Tract. Biochemical Society Transactions, 48, 327-336. [Google Scholar] [CrossRef] 
[15] Ma, J., Rubin, B.K. and Voynow, J.A. (2018) Mucins, Mucus, and Goblet Cells. Chest Journal, 154, 169-176. [Google Scholar] [CrossRef] [PubMed]
[16] Loxham, M., Davies, D.E. and Blume, C. (2014) Epithelial Function and Dysfunction in Asthma. Clinical & Experimental Allergy, 44, 1299-1313. [Google Scholar] [CrossRef] [PubMed]
[17] Gon, Y. and Hashimoto, S. (2018) Role of Airway Epithelial Barrier Dysfunction in Pathogenesis of Asthma. Allergology International, 67, 12-17. [Google Scholar] [CrossRef] [PubMed]
[18] Campbell, H.K., Maiers, J.L. and DeMali, K.A. (2017) Interplay between Tight Junctions & Adherens Junctions. Experimental Cell Research, 358, 39-44. [Google Scholar] [CrossRef] [PubMed]
[19] Walko, G., Castañón, M.J. and Wiche, G. (2015) Molecular Architecture and Function of the Hemidesmosome. Cell and Tissue Research, 360, 529-544. [Google Scholar] [CrossRef] [PubMed]
[20] Georas, S.N. and Rezaee, F. (2014) Epithelial Barrier Function: At the Front Line of Asthma Immunology and Allergic Airway Inflammation. The Journal of Allergy and Clinical Immunology, 134, 509-520. [Google Scholar] [CrossRef] [PubMed]
[21] Nawijn, M.C., Hackett, T.L., Postma, D.S., et al. (2011) E-Cadherin: Gatekeeper of Airway Mucosa and Allergic Sensitization. Trends in Immunology, 32, 248-255. [Google Scholar] [CrossRef] [PubMed]
[22] Jacquet, A. (2011) Interactions of Airway Epithelium with Protease Allergens in the Allergic Response. Clinical & Experimental Allergy, 41, 305-311. [Google Scholar] [CrossRef] [PubMed]
[23] Sajjan, U., et al. (2008) Rhinovirus Disrupts the Barrier Function of Polarized Airway Epithelial Cells. American Journal of Respiratory and Critical Care Medicine, 178, 1271-1281. [Google Scholar] [CrossRef] 
[24] Shepley-Mc Taggart, A., Sagum, C.A., Oliva, I., et al. (2021) SARS-CoV-2 Envelope (E) Protein Interacts with PDZ-Domain-2 of Host Tight Junction Protein ZO1. PLoS ONE, 16, e0251955. [Google Scholar] [CrossRef] [PubMed]
[25] Martens, K., Pugin, B., De Boeck, I., et al. (2018) Probiotics for the Airways: Potential to Improve Epithelial and Immune Homeostasis. Allergy, 73, 1954-1963. [Google Scholar] [CrossRef] [PubMed]
[26] Forteza, R.M., Casalino-Matsuda, S.M., Falcon, N.S., et al. (2012) Hyaluronan and Layilin Mediate Loss of Airway Epithelial Barrier Function Induced by Cigarette Smoke by Decreasing E-Cadherin. Journal of Biological Chemistry, 287, 42288-42298. [Google Scholar] [CrossRef] 
[27] Yamamoto, N., et al. (2021) Incense Smoke-Induced Oxidative Stress Disrupts Tight Junctions and Bronchial Epithelial Barrier Integrity and Induces Airway Hyperresponsiveness in Mouse Lungs. Scientific Reports, 11, Article No. 7222. [Google Scholar] [CrossRef] [PubMed]
[28] 崔海洋, 马壮, 孙文武. 冷空气诱发支气管哮喘的研究进展[J]. 中华肺部疾病杂志(电子版), 2016, 9(5): 558-561.
[29] Zhou, J., Zhou, X.D., Xu, R., et al. (2021) The Degradation of Airway Epithelial Tight Junctions in Asthma under High Airway Pressure Is Probably Mediated by Piezo-1. Frontiers in Physiology, 12, Article ID: 637790. [Google Scholar] [CrossRef] [PubMed]
[30] 李敏超, 尤列•皮尔曼, 周向东. MARCKS磷酸化对冷刺激诱导人气道上皮细胞MUC5AC分泌的影响[J]. 中南大学学报(医学版), 2012, 37(5): 447-452.
[31] Lambrecht, B.N. and Hammad, H. (2014) Immunology, Allergens and the Airway Epithelium Response: Gateway to Allergic Sensitization. The Journal of Allergy and Clinical Immunology, 134, 499-507. [Google Scholar] [CrossRef] [PubMed]
[32] Xiao, C., et al. (2011) Defective Epithelial Barrier Function in Asthma. The Journal of Allergy and Clinical Immunology, 128, 549-556.E12. [Google Scholar] [CrossRef] [PubMed]
[33] Sweerus, K., et al. (2017) Claudin-18 Deficiency Is Associated with Airway Epithelial Barrier Dysfunction and Asthma. The Journal of Allergy and Clinical Immunology, 139, 72-81.E1. [Google Scholar] [CrossRef] [PubMed]
[34] Lee, P.H., Kim, B.G., Lee, S.H., et al. (2018) Alteration in Claudin-4 Contributes to Airway Inflammation and Responsiveness in Asthma. Allergy, Asthma & Immunology Research, 10, 25-33.
[35] Kumamoto, J., Tsutsumi, M., Goto, M., et al. (2016) Japanese Cedar (Cryptomeria japonica) Pollen Allergen Induces Elevation of Intracellular Calcium in Human Keratinocytes and Impairs Epidermal Barrier Function of Human Skin ex Vivo. Archives of Dermatological Research, 308, 49-54. [Google Scholar] [CrossRef] [PubMed]
[36] Saito, T., Ichikawa, T., Numakura, T., et al. (2021) PGC-1α Regulates Airway Epithelial Barrier Dysfunction Induced by House Dust Mite. Respiratory Research, 22, Article No. 63. [Google Scholar] [CrossRef] [PubMed]
[37] 周峥嵘, 等. PGC-1α研究进展[J]. 江苏大学学报(医学版), 2018, 28(4): 362-366.
[38] Dong, H.M., Le, Y.Q., Wang, Y.H., et al. (2017) Extracellular Heat Shock Protein 90α Mediates HDM-Induced Bronchial Epithelial Barrier Dysfunction by Activating RhoA/MLC Signaling. Respiratory Research, 18, Article No. 111. [Google Scholar] [CrossRef] [PubMed]
[39] Rezaee, F., Meednu, N., Emo, J.A., et al. (2011) Polyinosinic: Polycytidylic Acid Induces Protein Kinase D-Dependent Disassembly of Apical Junctions and Barrier Dysfunction in Airway Epithelial Cells. The Journal of Allergy and Clinical Immunology, 128, 1216-1224.E11. [Google Scholar] [CrossRef] [PubMed]
[40] Kicic, A., et al. (2016) Impaired Airway Epithelial Cell Responses from Children with Asthma to Rhinoviral Infection. Clinical & Experimental Allergy, 46, 1441-1455. [Google Scholar] [CrossRef] [PubMed]
[41] Hasan, S., Sebo, P. and Osicka, R. (2018) A Guide to Polarized Airway Epithelial Models for Studies of Host-Pathogen Interactions. The FEBS Journal, 285, 4343-4358. [Google Scholar] [CrossRef] [PubMed]
[42] Wang, H., He, L., Liu, B., et al. (2018) Establishment and Comparison of Air-Liquid Interface Culture Systems for Primary and Immortalized Swine Tracheal Epithelial Cells. BMC Cell Biology, 19, Article No. 10. [Google Scholar] [CrossRef] [PubMed]
[43] Ladjemi, M., et al. (2018) Bronchial Epithelial IgA Secretion Is Impaired in Asthma. Role of IL-4/IL-13. American Journal of Respiratory and Critical Care Medicine, 197, 1396-1409. [Google Scholar] [CrossRef] 
[44] Hu, Y., et al. (2017) TSLP Signaling Blocking Alleviates E-Cadherin Dysfunction of Airway Epithelium in a HDM-Induced Asthma Model. Cellular Immunology, 315, 56-63. [Google Scholar] [CrossRef] [PubMed]
[45] 柴园园, 徐佳雨, 刘莉. 气道上皮细胞在哮喘肺部炎症中的屏障作用和免疫调节作用[J]. 医学综述, 2021, 27(13): 2509-2515.
[46] Sekiyama, A., Gon, Y., Terakedo, M., et al. (2012) Glucocorticoids Enhance Airway Epithelial Barrier Integrity. International Immunopharmacology, 12, 350-357. [Google Scholar] [CrossRef] [PubMed]
[47] Coraux, C., Kileztky, C., Polette, M., et al. (2004) Airway Epithelial Integrity Is Protected by a Long-Acting Beta2-Adrenergic Receptor Agonist. American Journal of Respiratory Cell and Molecular Biology, 30, 605-612. [Google Scholar] [CrossRef] 
[48] Trinh, H., Pham, D., Choi, Y., et al. (2018) Epithelial Folliculin Enhances Airway Inflammation in Aspirin-Exacerbated Respiratory Disease. Clinical & Experimental Allergy, 48, 1464-1473. [Google Scholar] [CrossRef] [PubMed]
[49] Yuan, X., Wang, J., Li, Y., et al. (2018) Allergy Immunotherapy Restores Airway Epithelial Barrier Dysfunction through Suppressing IL-25-Induced Endoplasmic Reticulum Stress in Asthma. Scientific Reports, 8, Article No. 7950. [Google Scholar] [CrossRef] [PubMed]
[50] Richards, L.B., Li, M., Folkerts, G., et al. (2020) Butyrate and Propionate Restore the Cytokine and House Dust Mite Compromised Barrier Function of Human Bronchial Airway Epithelial Cells. International Journal of Molecular Sciences, 22, Article No. 65. [Google Scholar] [CrossRef] [PubMed]

为你推荐