促炎因子高迁移率族蛋白盒(High Mobility Group Box Protein)是一种非组蛋白且普遍存在的染色体蛋白,富含构成高迁移率族蛋白家族一部分的活性染色质,由人类hmgb1基因(13q12)编码,特别是高迁移率族蛋白具有特定的基序,即脱氧核糖核酸结合域。高迁徙率族蛋白家族有四个成员(HMGB1-4),其中HMGB1蛋白(也称为HMG1、HMG-1、HMG 1、amphoterin、p30)是整个HMG家族蛋白中表达频率最高的。本文就HMGB1在呼吸系统疾病中的作用、应用和潜在的诊断应用作一综述,以期为上述疾病诊断和治疗提供新思路。
The proinflammatory factor high-mobility group box protein (HMGB) is a non-histone and ubiquitous chro-mosomal protein found enriched in active chromatin forming part of the high mobility group family of proteins and is encoded by the HMGB1 gene (13q12) in human. In particular HMGBs have specific motifs that are DNA-binding domains. The HMGBs are composed of four categories (HMGB1-4). HMGB1 (also known as HMG1, HMG-1, HMG 1, amphoterin, p30) is the most frequently expressed of the entire HMG family proteins. This review aim is to analyse advances on HMGB1 role, employment and potential diagnostic application in disease of respiratory system. It is expected to provide new ideas for the diagnosis and treatment of these diseases.
The proinflammatory factor high-mobility group box protein (HMGB) is a non-histone and ubiquitous chro-mosomal protein found enriched in active chromatin forming part of the high mobility group family of proteins and is encoded by the HMGB1 gene (13q12) in human. In particular HMGBs have specific motifs that are DNA-binding domains. The HMGBs are composed of four categories (HMGB1-4). HMGB1 (also known as HMG1, HMG-1, HMG 1, amphoterin, p30) is the most frequently expressed of the entire HMG family proteins. This review aim is to analyse advances on HMGB1 role, employment and potential diagnostic application in disease of respiratory system. It is expected to provide new ideas for the diagnosis and treatment of these diseases.
Keywords:HMGB1, Asthma, Pulmonary Fibrosis, COPD, Pneumonia, Lung Cancer
邵润玉,张彩莲,郭晋兰,李 欣,门 凯. 高迁移率族蛋白B1在呼吸系统疾病中的研究进展Research Progress of High-Mobility Group Box Protein B1 in Respiratory Diseases[J]. 临床医学进展, 2021, 11(11): 4976-4982. https://doi.org/10.12677/ACM.2021.1111731
参考文献ReferencesDi Candia, L., Gomez, E., Venereau, E., et al. (2017) HMGB1 Is Upregulated in the Airways in Asthma and Potentiates Airway Smooth Muscle Contraction via TLR4. Journal of Allergy and Clinical Immunology, 140, 584-587.
<br>https://doi.org/10.1016/j.jaci.2016.11.049Papi, A., Brightling, C., Pedersen, S.E., et al. (2018) Asthma. The Lancet, 391, 783-800.
<br>https://doi.org/10.1016/S0140-6736(17)33311-1Thomas, R., Paolo, S., Pierre-Olivier, B., et al. (2018) Diagnosis and Management of Asthma—The Swiss Guidelines. Respiration; International Review of Thoracic Diseases, 95, 364-380. <br>https://doi.org/10.1159/000486797Gong, F., Pan, Y.H., Huang, X., et al. (2017) From Bench to Bedside: Therapeutic Potential of Interleukin-9 in the Treatment of Asthma. Experimental and Therapeutic Medicine, 13, 389-394. <br>https://doi.org/10.3892/etm.2017.4024Marsh, A.M., Nguyen, A.H., Parker, T.M., et al. (2017) Clinical Use of High Mobility Group Box 1 and the Receptor for Advanced Glycation end Products in the Prognosis and Risk Stratification of Heart Failure: A Literature Review. Canadian Journal of Physiology and Pharmacology, 95, 253-259. <br>https://doi.org/10.1139/cjpp-2016-0299Liu, Y., Zhang, H., Ni, R., et al. (2017) IL-4R Suppresses Airway Inflammation in Bronchial Asthma by Inhibiting the IL-4/STAT6 Pathway. Pulmonary Pharmacology and Therapeutics, 43, 32-38.
<br>https://doi.org/10.1016/j.pupt.2017.01.006Chen, S., Wang, Y., Gong, G., et al. (2015) Ethyl Pyruvate Attenuates Murine Allergic Rhinitis Partly by Decreasing High Mobility Group Box 1 Release. Experimental Biology and Medicine, 240, 1490-1499.
<br>https://doi.org/10.1177/1535370214566563Hou, C., Kong, J., Liang, Y., et al. (2015) HMGB1 Contributes to Allergen-Induced Airway Remodeling in a Murine Model of Chronic Asthma by Modulating Airway Inflammation and Activating Lung Fibroblasts. Cellular & Molecular Immunology, 12, 409-423. <br>https://doi.org/10.1038/cmi.2014.60Shim, E.-J., Chun, E., Lee, H.-S., et al. (2012) The Role of High-Mobility Group Box-1 (HMGB1) in the Pathogenesis of Asthma. Clinical & Experimental Allergy, 42, 958-965. <br>https://doi.org/10.1111/j.1365-2222.2012.03998.x陈亚红. 2021年GOLD慢性阻塞性肺疾病诊断、治疗及预防全球策略解读[J]. 中国医学前沿杂志(电子版), 2021, 13(1): 16-37.Kim, V., Rogers, T.J. and Criner, G.J. (2008) New Concepts in the Pathobiology of Chronic Obstructive Pulmonary Disease. Proceedings of the American Thoracic Society, 5, 478-485. <br>https://doi.org/10.1513/pats.200802-014ETYang, H., et al. (2012) Novel Insights for High Mobility Group Box 1 Protein-Mediated Cellular Immune Response in Sepsis: A Systemic Review. World Journal of Emergency Medicine, 3, 165-171.
<br>https://doi.org/10.5847/wjem.j.issn.1920-8642.2012.03.001Huan, Y., Haichao, W. and Ulf, A. (2020) Targeting Inflammation Driven by Hmgb1. Frontiers in Immunology, 11, 484. <br>https://doi.org/10.3389/fimmu.2020.00484Shang, G.-H., Jia, C.-Q., Tian, H., et al. (2009) Serum High Mobility Group Box Protein 1 as a Clinical Marker for Non-Small Cell Lung Cancer. Respiratory Medicine, 103, 1949-1953. <br>https://doi.org/10.1016/j.rmed.2009.05.019Lee, H., Park, J., Kim, W.J., et al. (2017) Blockade of Rage Ameliorates Elastase-Induced Emphysema Development and Progression via Rage-Damp Signaling. The FASEB Journal, 31, 2076-2098.
<br>https://doi.org/10.1096/fj.201601155RLiu, W., Liu, Z.G., Zhang, W.D. and Cai, S.X. (2018) Ulinastatin Protects the Lungs of Copd Rats through the Hmgb1/tlr4 Signaling Pathway. Oncology Letters, 16, 4057-4063.Wang, C.M., Jiang, M. and Wang, H.J. (2013) Effect of NF-κB Inhibitor on High-Mobility Group Protein B1 Expression in a COPD Rat Model. Molecular Medicine Reports, 7, 499-502. <br>https://doi.org/10.3892/mmr.2012.1181Schwartz, D.A. (2016) Idopathich Pulmonary Fibrosis Is a Complex Genetic Disorder. Transactions of the American Clinical and Climatological Association, 127, 34-45.King, T.E., Pardo, A. and Selman, M. (2011) Idiopathic Pulmonary Fibrosis. The Lancet, 378, 1949-1961.
<br>https://doi.org/10.1016/S0140-6736(11)60052-4Li, L.-C., Gao, J. and Li, J. (2014) Emerging Role of HMGB1 in Fibrotic Diseases. Journal of Cellular and Molecular Medicine, 18, 2331-2339. <br>https://doi.org/10.1111/jcmm.12419Hubbard, R.B., Smith, C., Le Jeune, I., et al. (2008) The Association between Idiopathic Pulmonary Fibrosis and Vascular Disease. American Journal of Respiratory and Critical Care Medicine, 178, 1257-1261.
<br>https://doi.org/10.1164/rccm.200805-725OCSprunger, D.B., Olson, A.L., Huie, T.J., et al. (2012) Pulmonary Fibrosis Is Associated with an Elevated Risk of Thromboembolic Disease. European Respiratory Journal, 39, 125-132. <br>https://doi.org/10.1183/09031936.00041411Shigemitsu, H. and Azuma, A. (2011) Sarcoidosis and Interstitial Pulmonary Fibrosis; Two Distinct Disorders or Two Ends of the Same Spectrum. Current Opinion in Pulmonary Medicine, 17, 303-307.
<br>https://doi.org/10.1097/MCP.0b013e3283486d52Kim, D.E., Min, K., Kim, J.S., et al. (2012) High-Mobility Group Box-1 Protein Induces Mucin 8 Expression through the Activation of the JNK and PI3K/Akt Signal Pathways in Human Airway Epithelial Cells. Biochemical and Biophysical Research Communications, 421, 436-441. <br>https://doi.org/10.1016/j.bbrc.2012.03.131Wang, Q., Wang, J., Wang, J., et al. (2017) HMGB1 Induces Lung Fibroblast to Myofibroblast Differentiation through NF-κB-Mediated TGF-β1 Release. Molecular Medicine Reports, 15, 3062-3068.
<br>https://doi.org/10.3892/mmr.2017.6364He, M., Kubo, H., Ishizawa, K., et al. (2007) The Role of the Receptor for Advanced Glycation EN-Products in Lung Fibrosis. The American Journal of Physiology-Lung Cellular and Molecular Physiology, 293, L1427-L1436.
<br>https://doi.org/10.1152/ajplung.00075.2007Pedroza, M., Le, T.T., Lewis, K., et al. (2016) STAT-3 Contributes to Pulmonary Fibrosis through Epithelial Injury and Fibroblast-Myofibroblast Differentiation. FASEB Journal, 30, 129-140. <br>https://doi.org/10.1096/fj.15-273953Tang, L.-Y., Heller, M., Meng, Z., et al. (2017) Transforming Growth Factor-β (TGF-β) Directly Activates the JAK1-STAT3 Axis to Induce Hepatic Fibrosis in Coordination with the SMAD Pathway. Journal of Biological Chemistry, 292, 4302-4312. <br>https://doi.org/10.1074/jbc.M116.773085Li, C., Yu, Y., Li, W., et al. (2017) Phycocyanin Attenuates Pulmonary Fibrosis via the TLR2-MyD88-NF-κB Signaling Pathway. Scientific Reports, 7, Article No. 5843. <br>https://doi.org/10.1038/s41598-017-06021-5Hamada, N., Maeyama, T., Kawaguchi, T., et al. (2008) The Role of High Mobility Group Box1 in Pulmonary Fibrosis. American Journal of Respiratory Cell and Molecular Biology, 39, 440-447.
<br>https://doi.org/10.1165/rcmb.2007-0330OCGrief, S.N. and Loza, J.K. (2018) Guidelines for the Evaluation and Treatment of Pneumonia. Primary Care: Clinics in Office Practice, 45, 485-503. <br>https://doi.org/10.1016/j.pop.2018.04.001López Del Prado, G.R., Hernán García, C., Moreno Cea, L., et al. (2014) Malaria in Developing Countries. The Journal of Infection in Developing Countries, 8, 1-4. <br>https://doi.org/10.3855/jidc.4610Barbier, F. andremont, A., Wolff, M., et al. (2013) Hospital-Acquired Pneumonia and Ventilator-Associated Pneumonia: Recent Advances in Epidemiology and Management. Current Opinion in Pulmonary Medicine, 19, 216-228.
<br>https://doi.org/10.1097/MCP.0b013e32835f27beOttosen, J. and Evans, H. (2014) Pneumonia: Challenges in the Definition, Diagnosis, and Management of Disease. Surgical Clinics of North America, 94, 1305-1317. <br>https://doi.org/10.1016/j.suc.2014.09.001Ding, Y., Chu, C., Li, Y.Q., et al. (2018) High Expression of HMGB1 in Children with Refractory Mycoplasma pneumoniae Pneumonia. BioMed Central, 18, 439. <br>https://doi.org/10.1186/s12879-018-3346-8Tang, Z., Zang, N., Fu, Y., et al. (2018) HMGB1 Mediates HAdV-7 Infection-Induced Pulmonary Inflammation in Mice. Biochemical and Biophysical Research Communications, 501, 1-8. <br>https://doi.org/10.1016/j.bbrc.2018.03.145Morbini, P., Villa, C., Campo, I., et al. (2006) The Receptor for Advanced Glycation end Products and Its Ligands: A New Inflammatory Pathway in Lung Disease? Modern Pathology, 19, 1437-1445.
<br>https://doi.org/10.1038/modpathol.3800661Alpkvist, H., Athlin, S., Mölling, P., et al. (2018) High HMGB1 Levels in Sputum Are Related to Pneumococcal Bacteraemia But Not to Disease Severity in Community-Acquired Pneumonia. Scientific Reports, 8, Article No. 13428.
<br>https://doi.org/10.1038/s41598-018-31504-4Wang, H.-L., Tsao, S.-M., Yeh, C.-B., et al. (2017) Circulating Level of High Mobility Group Box-1 Predicts the Severity of Community-Acquired Pneumonia: Regulation of Inflammatory Responses via the c-Jun N-Terminal Signaling Pathway in Macrophages. Molecular Medicine Reports, 16, 2361-2366. <br>https://doi.org/10.3892/mmr.2017.6892Hou, X.Q., Qin, J.L., Zheng, X.X., et al. (2014) Potential Role of High-Mobility Group Box 1 Protein in the Pathogenesis of Influenza H5N1 Virus Infection. Acta Virologica, 58, 69-75. <br>https://doi.org/10.4149/av_2014_01_69Ettinger, D.S., Wood, D.E., Akerley, W., et al. (2016) NCCN Guidelines Insights: Non-Small Cell Lung Cancer, Version 4. Journal of the National Comprehensive Cancer Network, 14, 255-264. <br>https://doi.org/10.6004/jnccn.2016.0031Herbst, R.S., Morgensztern, D., et al. (2018) The Biology and Management of Non-Small Cell Lung Cancer. Nature: International Weekly Journal of Science, 553, 446-454. <br>https://doi.org/10.1038/nature25183Wu, L. and Yang, L. (2018) The Function and Mechanism of HMGB1 in Lung Cancer and Its Potential Therapeutic Implications. Oncology Letters, 15, 6799-6805. <br>https://doi.org/10.3892/ol.2018.8215Taguchi, A., Blood, D.C., del Toro, G., et al. (2000) Blockade of RAGE-Amphoterin Signalling Suppresses Tumour Growth and Metastases. Nature, 405, 354-360. <br>https://doi.org/10.1038/35012626Niki, M., Yokoi, T., Kurata, T., et al. (2017) New Prognostic Biomarkers and Therapeutic Effect of Bevacizumab for Patients with Non-Small-Cell Lung Cancer. Lung Cancer: Targets and Therapy, 8, 91-99.
<br>https://doi.org/10.2147/LCTT.S138887Shang, G.-H., Jia, C.-Q., Tian, H., et al. (2009) Serum High Mobility Group Box Protein 1 as a Clinical Marker for Non-Small Cell Lung Cancer. Respiratory Medicine, 103, 1949-1953. <br>https://doi.org/10.1016/j.rmed.2009.05.019Carmeliet, P. (2005) Angiogenesis in Life, Disease and Medicine. Nature: International Weekly Journal of Science, 438, 932-936. <br>https://doi.org/10.1038/nature04478Pan, B., Chen, D., Huang, J., et al. (2014) HMGB1-Mediated Autophagy Promotes Docetaxel Resistance in Human Lung Adenocarcinoma. Molecular Cancer, 13, 165. <br>https://doi.org/10.1186/1476-4598-13-165