白癜风发病机制复杂,涉及多种学说。氧化应激和自身免疫作为白癜风形成与发展的重要机制,两者相互影响,贯穿疾病整个进程的始终。现有研究表明,部分黑素细胞特异性自身免疫的活化由氧化应激诱发。高迁移率族蛋白1作为氧化应激与自身免疫联系的重要分子,近来被发现参与白癜风发病过程。本文将结合近年来的研究进展,对高迁移率族蛋白1在白癜风发病中的作用进行综述,为靶向治疗提供新的突破点。
The pathogenesis of vitiligo is complex and involves many theories. As the important mechanisms of vitiligo occurrence and progression, oxidative stress and autoimmunity influence each other throughout the whole process of the disease. Existing studies suggest that some melanocyte-specific autoimmunity activation is induced by oxidative stress. HMGB1, as important molecule that links oxidative stress and autoimmunity, has recently been found to be involved in the pathogenesis of vitiligo. This article will briefly review the research progress on the role of HMGB1 in vitiligo to provide a breakthrough for targeted therapy.
Children’s Hospital of Chongqing Medical University, National Clinical Research Center for Child Health and Disorders, Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing Key Laboratory of Pediatrics, Chongqing
Received: Apr. 22nd, 2022; accepted: May 9th, 2022; published: May 16th, 2022
ABSTRACT
The pathogenesis of vitiligo is complex and involves many theories. As the important mechanisms of vitiligo occurrence and progression, oxidative stress and autoimmunity influence each other throughout the whole process of the disease. Existing studies suggest that some melanocyte-specific autoimmunity activation is induced by oxidative stress. HMGB1, as important molecule that links oxidative stress and autoimmunity, has recently been found to be involved in the pathogenesis of vitiligo. This article will briefly review the research progress on the role of HMGB1 in vitiligo to provide a breakthrough for targeted therapy.
冯丁夏,肖异珠. 高迁移率族蛋白1在白癜风中的研究进展Research Advances of HMGB1 in Vitiligo[J]. 生物医学, 2022, 12(03): 143-149. https://doi.org/10.12677/HJBM.2022.123018
参考文献References王晓艳, 王婷琳, 周城, 等. 中国六省市白癜风流行病学调查[J]. 中华皮肤科杂志, 2010, 43(7): 463-466.Jadeja, S.D., Mayatra, J.M., Vaishnav, J., et al. (2021) A Concise Review on the Role of Endoplasmic Reticulum Stress in the Development of Autoimmunity in Vitiligo Pathogenesis. Frontiers in Immunology, 11, Article ID: 624566.
<br>https://doi.org/10.3389/fimmu.2020.624566Blair, R.H., Horn, A.E., Pazhani, Y., et al. (2016) The HMGB1 C-Terminal Tail Regulates DNA Bending. Journal of Molecular Biology, 428, 4060-4072. <br>https://doi.org/10.1016/j.jmb.2016.08.018Yang, H., Lundbäck, P., Ottosson, L., et al. (2021) Redox Modifications of Cysteine Residues Regulate the Cytokine Activity of HMGB1. Molecular Medicine, 27, 58. <br>https://doi.org/10.1186/s10020-021-00307-1Senda, N., Yanai, H., Hibino, S., et al. (2021) HMGB1-Mediated Chromatin Remodeling Attenuates IL24 Gene Expression for the Protection from Allergic Contact Dermatitis. Proceedings of the National Academy of Sciences, 118, e2022343118. <br>https://doi.org/10.1073/pnas.2022343118Kim, Y.H., Kwak, M.S., Park, J.B., et al. (2016) N-Linked Glycosylation Plays a Crucial Role in the Secretion of HMGB1. Journal of Cell Science, 129, 29. <br>https://doi.org/10.1242/jcs.176412Kwak, M.S., Kim, H.S., Lee, B., et al. (2020) Immunological Significance of HMGB1 Post-Translational Modification and Redox Biology. Frontiers in Immunology, 11, Article No. 1189. <br>https://doi.org/10.3389/fimmu.2020.01189Tang, D., Kang, R., Livesey, K.M., et al. (2010) Endogenous HMGB1 Regulates Autophagy. Journal of Cell Biology, 190, 881-892. <br>https://doi.org/10.1083/jcb.200911078Huebener, P., Gwak, G.Y., Pradere, J.P., et al. (2014) High-Mobility Group Box 1 Is Dispensable for Autophagy, Mitochondrial Quality Control, and Organ Function in Vivo. Cell Metabolism, 19, 539-547.
<br>https://doi.org/10.1016/j.cmet.2014.01.014Yu, R., Yang, D., Lei, S., et al. (2015) HMGB1 Promotes Hepatitis c Virus Replication by Interaction with Stem-Loop 4 in the Viral 5’ Untranslated Region. Journal of Virology, 90, 2332-2344. <br>https://doi.org/10.1128/JVI.02795-15Paudel, Y.N., Angelopoulou, E., Piperi, C., et al. (2019) Enlightening the Role of High Mobility Group Box 1 (HMGB1) in Inflammation: Updates on Receptor Signaling. European Journal of Pharmacology, 858, Article ID: 172487.
<br>https://doi.org/10.1016/j.ejphar.2019.172487Nakamura, Y., Fukuta, A., Miyashita, K., et al. (2021) Perineural High-Mobility Group Box 1 Induces Mechanical Hypersensitivity through Activation of Spinal Microglia: Involvement of Glutamate-NMDA Receptor Dependent Mechanism in Spinal Dorsal Horn. Biochemical Pharmacology, 186, Article ID: 114496.
<br>https://doi.org/10.1016/j.bcp.2021.114496Zuo, T., Yue, Y., Wang, X., et al. (2021) Luteolin Relieved DSS-Induced Colitis in Mice via HMGB1-TLR-NF-κB Signaling Pathway. Inflammation, 44, 570-579. <br>https://doi.org/10.1007/s10753-020-01354-2Fan, H., Tang, H.B., Chen, Z., et al. (2020) Inhibiting HMGB1-RAGE Axis Prevents Pro-Inflammatory Macrophages/microglia Polarization and Affords Neuroprotection after Spinal Cord Injury. Journal of Neuroinflammation, 17, 295. <br>https://doi.org/10.1186/s12974-020-01973-4He, C., Sun, S., Zhang, Y., et al. (2021) The Role of Irreversible Electroporation in Promoting M1 Macrophage Polarization via Regulating the HMGB1-RAGE-MAPK Axis in Pancreatic Cancer. Oncoimmunology, 10, Article ID: 1897295.
<br>https://doi.org/10.1080/2162402X.2021.1897295Feng, X., Yang, R., Tian, Y., et al. (2020) HMGB1 Protein Promotes Glomerular Mesangial Matrix Deposition via TLR2 in Lupus Nephritis. Journal of Cellular Physiology, 235, 5111-5119. <br>https://doi.org/10.1002/jcp.29379Wang, X., Li, Z., Bai, Y., et al. (2021) A Small Molecule Binding HMGB1 Inhibits Caspase-11-Mediated Lethality in Sepsis. Cell Death & Disease, 12, 402. <br>https://doi.org/10.1038/s41419-021-03652-5Ning, J., Yang, R., Wang, H., et al. (2021) HMGB1 Enhances Chemotherapy Resistance in Multiple Myeloma Cells by Activating the Nuclear Factor-κB Pathway. Experimental and Therapeutic Medicine, 22, 705.
<br>https://doi.org/10.3892/etm.2021.10137Li, B., Yi, X., Zhuang, T., et al. (2021) RIP1-Mediated Necroptosis Facilitates Oxidative Stress-Induced Melanocyte Death, Offering Insight into Vitiligo. Journal of Investigative Dermatology, 141, 2921-2931.
<br>https://doi.org/10.1016/j.jid.2020.06.042Wahid, A., Chen, W., Wang, X., et al. (2021) High-Mobility Group Box 1 Serves as an Inflammation Driver of Cardiovascular Disease. Biomedicine & Pharmacotherapy, 139, Article ID: 111555.
<br>https://doi.org/10.1016/j.biopha.2021.111555Wang, Z., Zhou, H., Zheng, H., et al. (2021) Autophagy-Based Unconventional Secretion of HMGB1 by Keratinocytes Plays a Pivotal Role in Psoriatic Skin Inflammation. Autophagy, 17, 529-552.
<br>https://doi.org/10.1080/15548627.2020.1725381Kim, J.Y., Lee, E.J., Seo, J., et al. (2017) Impact of High-Mobility Group Box 1 on Melanocytic Survival and Its Involvement in the Pathogenesis of Vitiligo. British Journal of Dermatology, 176, 1558-1568.
<br>https://doi.org/10.1111/bjd.15151Cui, T., Zhang, W., Li, S., et al. (2019) Oxidative Stress-Induced HMGB1 Release from Melanocytes: A Paracrine Mechanism Underlying the Cutaneous Inflammation in Vitiligo. Journal of Investigative Dermatology, 139, 2174-2184.
<br>https://doi.org/10.1016/j.jid.2019.03.1148Mou, K., Liu, W., Miao, Y., et al. (2018) HMGB1 Deficiency Reduces H2O2-Induced Oxidative Damage in Human Melanocytes via the Nrf2 Pathway. Journal of Cellular and Molecular Medicine, 22, 6148-6156.
<br>https://doi.org/10.1111/jcmm.13895Jian, Z., Li, K., Song, P., et al. (2014) Impaired Activation of the Nrf2-ARE Signaling Pathway Undermines H2O2-Induced Oxidative Stress Response: A Possible Mechanism for Melanocyte Degeneration in Vitiligo. Journal of Investigative Dermatology, 134, 2221-2230. <br>https://doi.org/10.1038/jid.2014.152Li, S., Zhu, G., Yang, Y., et al. (2017) Oxidative Stress Drives CD8+ T-Cell Skin Trafficking in Patients with Vitiligo through CXCL16 Upregulation by Activating the Unfolded Protein Response in Keratinocytes. Journal of Allergy and Clinical Immunology, 140, 177-189.e9. <br>https://doi.org/10.1016/j.jaci.2016.10.013陈红. 氧化应激下白癜风黑素细胞转染HMGB1相关变化研究[D]: [硕士学位论文]. 张家口: 河北北方学院, 2019.Lv, R., Du, L., Liu, X., et al. (2019) Rosmarinic Acid Attenuates Inflammatory Responses through Inhibiting HMGB1/TLR4/NF-κB Signaling Pathway in a Mouse Model of Parkinson’s Disease. Life Sciences, 223, 158-165.
<br>https://doi.org/10.1016/j.lfs.2019.03.030Zhao, G., Fu, C., Wang, L., et al. (2017) Down-Regulation of Nuclear HMGB1 Reduces Ischemia-Induced HMGB1 Translocation and Release and Protects against Liver Ischemia-Reperfusion Injury. Scientific Reports, 7, Article No. 46272. <br>https://doi.org/10.1038/srep46272Chen, G., Hou, Y., Li, X., et al. (2021) Sepsis-Induced Acute Lung Injury in Young Rats Is Relieved by Calycosin through Inactivating the HMGB1/MyD88/NF-κB Pathway and NLRP3 Inflammasome. International Immunopharmacology, 96, Article ID: 107623. <br>https://doi.org/10.1016/j.intimp.2021.107623Harris, J.E., Harris, T.H., Weninger, W., et al. (2012) A Mouse Model of Vitiligo with Focused Epidermal Depigmentation Requires IFN-γ for Autoreactive CD8⁺ T-Cell Accumulation in the Skin. Journal of Investigative Dermatology, 132, 1869-1876. <br>https://doi.org/10.1038/jid.2011.463Kim, S.R., Heaton, H., Liu, L.Y., et al. (2018) Rapid Repigmentation of Vitiligo Using Tofacitinib plus Low-Dose, Narrowband UV-B Phototherapy. JAMA Dermatology, 154, 370-371. <br>https://doi.org/10.1001/jamadermatol.2017.5778Joshipura, D., Alomran, A., Zancanaro, P., et al. (2018) Treatment of Vitiligo with the Topical Janus Kinase Inhibitor Ruxolitinib: A 32-Week Open-Label Extension Study with Optional Narrow-Band Ultraviolet B. Journal of the American Academy of Dermatology, 78, 1205-1207.e1. <br>https://doi.org/10.1016/j.jaad.2018.02.023He, S., Xu, J. and Wu, J. (2022) The Promising Role of Chemokines in Vitiligo: From Oxidative Stress to the Autoimmune Response. Oxidative Medicine and Cellular Longevity, 2022, Article ID: 8796735.
<br>https://doi.org/10.1155/2022/8796735