激酶与外周神经损伤修复研究进展
Research on Kinases and Peripheral Nerve Injury Repair
DOI: 10.12677/BP.2021.114012, PDF,    科研立项经费支持
作者: 张守萍, 关晋东, 孙 诚*, 刘晓宇*:南通大学,教育部/江苏省神经再生重点实验室/神经再生协同创新中心,江苏 南通
关键词: 激酶外周神经损伤修复炎症反应细胞凋亡 Kinase Peripheral Nerve Injury Repair In-flammatory Response Apoptosis
摘要: 外周神经损伤脱髓鞘疾病是最常见的外伤疾病。目前常见的治疗手段有外科手术缝合、自体神经或者异体神经移植及组织工程技术。影响损伤神经后期功能恢复因素众多如受损神经横断面积,缺损神经缺口长度及各种激酶、生长因子等表达的差异。激酶种类众多,作为重要的信号传导分子调控多条信号通路,包括神经损伤后坏死组织清除与神经再生等多种过程。因此,为进一步了解激酶在外周神经损伤修复中扮演的角色,本文回顾了多种常见的激酶类型、不同的神经损伤类型及其修复的进程,发现激酶可以通过调节自噬过程、炎症反应、细胞凋亡、细胞周期以及氧化应激等过程参与损伤神经组织再生修复微环境的形成,影响神经的再生修复。
Abstract: Peripheral nerve injury demyelinating disease is the most common traumatic disease. At present, common treatment methods include surgical suture, autologous nerve or allogeneic nerve transplantation and tissue engineering technology. There are many factors that affect the functional recovery of injured nerves, such as the cross-sectional area of the injured nerve, the length of the defect of the nerve and the difference in the expression of various kinases and growth factors. There are many kinds of kinases, which are important signal transduction molecules to regulate multiple signal pathways, and regulate various processes, such as the removal of necrotic tissue and nerve regeneration after nerve injury. Therefore, in order to further understand the role of kinases in the repair of peripheral nerve damage, this article reviews a variety of common kinase types, different types of nerve damage and their repair processes. We found that kinases can regulate processes, such as autophagy, inflammatory response, cell apoptosis, cell cycle and oxidative stress, and participate in the formation of the microenvironment for regeneration and repair of damaged nerve tissue through these processes, and affect the regeneration and repair of nerves.
文章引用:张守萍, 关晋东, 孙诚, 刘晓宇. 激酶与外周神经损伤修复研究进展[J]. 生物过程, 2021, 11(4): 99-108. https://doi.org/10.12677/BP.2021.114012

参考文献

[1] 关晋东, 等. G蛋白耦联胆汁酸受体激动剂INT777通过激活AMPK信号通路抑制施万细胞成髓鞘过程[J]. 南通大学学报(医学版), 2021, 41(1): 6-10.
[2] Niemi, J.P., et al. (2013) A Critical Role for Macrophages near Axotomized Neuronal Cell Bodies in Stimulating Nerve Regeneration. Journal of Neuroscience, 33, 16236-16248. [Google Scholar] [CrossRef
[3] Wu, D. and Murashov, A.K. (2013) Molecular Mecha-nisms of Peripheral Nerve Regeneration: Emerging Roles of Micrornas. Frontiers in Physiology, 4, 55. [Google Scholar] [CrossRef] [PubMed]
[4] 宋凯凯, 张锴, 贾龙. 周围神经系统损伤的微环境与修复方式[J]. 中国组织工程研究, 2021, 25(4): 651-656.
[5] Juerd, W., Alexandra, B. and Nens, V.A. (2020) Nerve Ultra-sound in Traumatic and Iatrogenic Peripheral Nerve Injury. Diagnostics (Basel, Switzerland), 11, 30. [Google Scholar] [CrossRef] [PubMed]
[6] Ketan, D., et al. (2019) Injection-Related Iatrogenic Peripheral Nerve Injuries: Surgical Experience of 354 Operated Cases. Neurology India, 67, S82-S91. [Google Scholar] [CrossRef] [PubMed]
[7] Tatsuya, H., et al. (2020) Iatrogenic Peripheral Nerve Inju-ries—Common Causes and Treatment: A Retrospective Single-Center Cohort Study. Journal of Orthopaedic Science. [Google Scholar] [CrossRef] [PubMed]
[8] 王轩, 利春叶. 医源性周围神经损伤的研究进展[J]. 医学综述, 2013, 19(23): 4302-4305.
[9] 吴剑彬, 等. 不同手术入路MIPO技术治疗肱骨干骨折时医源性桡神经损伤的风险研究[J]. 中国现代医生, 2017, 55(21): 66-72.
[10] Gu, X., Ding, F. and Williams, D.F. (2014) Neural Tissue En-gineering Options for Peripheral Nerve Regeneration. Biomaterials, 35, 6143-6156. [Google Scholar] [CrossRef] [PubMed]
[11] Baradaran, A., et al. (2021) Peripheral Nerve Healing: So Near and Yet So Far. Seminars in Plastic Surgery, 35, 204-210. [Google Scholar] [CrossRef] [PubMed]
[12] Scheib, J. and Hoke, A. (2013) Advances in Peripheral Nerve Re-generation. Nature Reviews Neurology, 9, 668-676. [Google Scholar] [CrossRef] [PubMed]
[13] Siqueira Mietto, B., et al. (2015) Role of IL-10 in Resolution of In-flammation and Functional Recovery after Peripheral Nerve Injury. Journal of Neuroscience, 35, 16431-16442. [Google Scholar] [CrossRef
[14] Wu, P., Nielsen, T.E. and Clausen, M.H. (2015) FDA-Approved Small-Molecule Kinase Inhibitors. Trends in Pharmacological Sciences, 36, 422-439. [Google Scholar] [CrossRef] [PubMed]
[15] Buttner, R., et al. (2018) Inflammaging Impairs Peripheral Nerve Maintenance and Regeneration. Aging Cell, 17, e12833. [Google Scholar] [CrossRef] [PubMed]
[16] Kanngiesser, M., et al. (2012) Inhibitor Kappa B Kinase Beta Dependent Cytokine Upregulation in Nociceptive Neurons Contributes to Nociceptive Hypersensitivity after Sciatic Nerve Injury. The Journal of Pain, 13, 485-497. [Google Scholar] [CrossRef] [PubMed]
[17] Roskoski, R. (2020) Properties of FDA-Approved Small Molecule Protein Kinase Inhibitors: A 2020 Update. Pharmacological Research, 152, Article ID: 104609. [Google Scholar] [CrossRef] [PubMed]
[18] Johnson, L.N. and Lewis, R.J. (2001) Structural Basis for Control by Phosphorylation. Chemical Reviews, 101, 2209-2242. [Google Scholar] [CrossRef] [PubMed]
[19] Solassol, I., Pinguet, F. and Quantin, X. (2019) FDA- and EMA-Approved Tyrosine Kinase Inhibitors in Advanced EGFR-Mutated Non-Small Cell Lung Cancer: Safety, Tolerability, Plasma Con-centration Monitoring, and Management. Biomolecules, 9, 668. [Google Scholar] [CrossRef] [PubMed]
[20] Yamauchi, K. (1999) Serine-Threonine Kinase. Nihon Rinsho, 57, 458-461.
[21] Jiao, Q., et al. (2018) Advances in Studies of Tyrosine Kinase Inhibitors and Their Acquired Resistance. Molecular Cancer, 17, 36. [Google Scholar] [CrossRef] [PubMed]
[22] Attwood, P.V. (2013) Histidine Ki-nases from Bacteria to Humans. Biochemical Society Transactions, 41, 1023-1028. [Google Scholar] [CrossRef
[23] 郑超, 李登高, 白薇. 植物富含半胱氨酸的类受体激酶的研究进展[J]. 生物技术通报, 2016, 32(11): 10-17.
[24] Lee, D.S., et al. (2017) The Arabidopsis Cysteine-Rich Receptor-Like Kinase CRK36 Regulates Immunity through Interaction with the Cytoplasmic Kinase BIK1. Frontiers in Plant Science, 8, 1856. [Google Scholar] [CrossRef] [PubMed]
[25] 杨宇亭, 闵伟红. 天冬氨酸激酶代谢调控的研究进展[J]. 食品科学, 2016, 37(7): 270-275.
[26] Makafe, G.G., et al. (2019) Quinoline Derivatives Kill Mycobacterium tuberculosis by Activating Glutamate Kinase. Cell Chemical Biology, 26, 1187-1194.e5. [Google Scholar] [CrossRef] [PubMed]
[27] Taylor, S.S., et al. (2012) Assembly of Allosteric Macromo-lecular Switches: Lessons from PKA. Nature Reviews Molecular Cell Biology, 13, 646-658. [Google Scholar] [CrossRef] [PubMed]
[28] Miyahara, T., et al. (2018) Propofol Induced Diverse and Subtype-Specific Translocation of PKC Families. Journal of Pharmacological Sciences, 137, 20-29. [Google Scholar] [CrossRef] [PubMed]
[29] Ferrer, I., et al. (2001) Phosphorylated Mitogen-Activated Protein Kinase (MAPK/ERK-P), Protein Kinase of 38 kDa (p38-P), Stress-Activated Protein Kinase (SAPK/JNK-P), and Cal-cium/Calmodulin-Dependent Kinase II (CaM Kinase II) Are Differentially Expressed in Tau Deposits in Neurons and Glial Cells in Tauopathies. Journal of Neural Transmission (Vienna), 108, 1397-1415. [Google Scholar] [CrossRef] [PubMed]
[30] Guo, Y.J., et al. (2020) ERK/MAPK Signalling Pathway and Tumor-igenesis. Experimental and Therapeutic Medicine, 19, 1997-2007. [Google Scholar] [CrossRef] [PubMed]
[31] Fang, J.Y. and Richardson, B.C. (2005) The MAPK Signalling Path-ways and Colorectal Cancer. The Lancet Oncology, 6, 322-327. [Google Scholar] [CrossRef
[32] Gaestel, M. (2015) MAPK-Activated Protein Kinases (MKs): Novel Insights and Challenges. Frontiers in Cell and Developmental Biology, 3, 88. [Google Scholar] [CrossRef] [PubMed]
[33] Bengal, E., Aviram, S. and Hayek, T. (2020) p38 MAPK in Glucose Metabolism of Skeletal Muscle: Beneficial or Harmful? International Journal of Molecular Sciences, 21, 6480. [Google Scholar] [CrossRef] [PubMed]
[34] Anne, S.L., et al. (2013) WNT3 Inhibits Cerebellar Granule Neuron Progenitor Proliferation and Medulloblastoma Formation via MAPK Activation. PLoS ONE, 8, e81769. [Google Scholar] [CrossRef] [PubMed]
[35] Xu, D., et al. (2018) TBK1 Suppresses RIPK1-Driven Apopto-sis and Inflammation during Development and in Aging. Cell, 174, 1477-1491.e19. [Google Scholar] [CrossRef] [PubMed]
[36] Parker, P.J. and Ullrich, A. (1987) Protein Kinase C. Journal of Cellular Physiology, 5, 53-56. [Google Scholar] [CrossRef] [PubMed]
[37] Soderling, T.R. (1999) The Ca-Calmodulin-Dependent Protein Kinase Cascade. Trends in Biochemical Sciences, 24, 232-236. [Google Scholar] [CrossRef
[38] Turnham, R.E. and Scott, J.D. (2016) Protein Kinase A Cat-alytic Subunit Isoform PRKACA; History, Function and Physiology. Gene, 577, 101-108. [Google Scholar] [CrossRef] [PubMed]
[39] 范衡宇, 佟超, 孙青原. 核糖体S6蛋白激酶p90~(rsk)与卵母细胞减数分裂[J]. 生物化学与生物物理进展, 2002(4): 506-509.
[40] 高磊, 等. CDKs(细胞周期依赖性蛋白激酶)调控细胞周期中的作用[J]. 畜牧兽医杂志, 2010, 29(2): 41-42+45.
[41] 田翠孟, 魏素菊. 细胞周期蛋白依赖性激酶与肿瘤关系的研究进展[J]. 实用肿瘤杂志, 2010, 25(4): 499-502.
[42] 王海青, 郭瑞珍. RAS-RAF-MEKl/2/-ERKl/2 MAPK信号转导通路及其与皮肤肿瘤的关系[J]. 中国皮肤性病学杂志, 2013, 27(2): 201-203+207.
[43] Neet, K. and Hunter, T. (1996) Vertebrate Non-Receptor Protein-Tyrosine Kinase Families. Genes Cells, 1, 147-169. [Google Scholar] [CrossRef] [PubMed]
[44] Eckhart, W., Hutchinson, M.A. and Hunter, T. (1979) An Activity Phosphorylating Tyrosine in Polyoma T Antigen Immunoprecipitates. Cell, 18, 925-933. [Google Scholar] [CrossRef] [PubMed]
[45] Hunter, T. (2008) Tony Hunter: Kinase King. Interview by Ruth Williams. Journal of Cell Biology, 181, 572-573. [Google Scholar] [CrossRef] [PubMed]
[46] Amatu, A., et al. (2019) Tropomyosin Receptor Kinase (TRK) Biology and the Role of NTRK Gene Fusions in Cancer. Annals of Oncology, 30, viii5-viii15. [Google Scholar] [CrossRef] [PubMed]
[47] Hirose, M., Kuroda, Y. and Murata, E. (2016) NGF/TrkA Signaling as a Therapeutic Target for Pain. Pain Practice, 16, 175-182. [Google Scholar] [CrossRef] [PubMed]
[48] 王从容, 等. 饮食脂肪含量和耐力运动对肥胖鼠胰岛素受体酪氨酸蛋白激酶的影响[J]. 体育科学, 2000(6): 51-54.
[49] Ja-cobsen, F.A., et al. (2018) A Role for the Non-Receptor Tyrosine Kinase Abl2/Arg in Experimental Neuroinflammation. Journal of Neuroimmune Pharmacology, 13, 265-276. [Google Scholar] [CrossRef] [PubMed]
[50] Wilson, J.E., et al. (2015) Inflammasome-Independent Role of AIM2 in Suppressing Colon Tumorigenesis via DNA-PK and Akt. Nature Medicine, 21, 906-913. [Google Scholar] [CrossRef] [PubMed]
[51] Wolanin, P.M., Thomason, P.A. and Stock, J.B. (2002) Histidine Protein Kinases: Key Signal Transducers outside the Animal Kingdom. Genome Biology, 3, REVIEWS3013. [Google Scholar] [CrossRef] [PubMed]
[52] Kreikemeyer, B., et al. (2001) Group A Streptococcal growth Phase-Associated Virulence Factor Regulation by a Novel Operon (Fas) with Homologies to Two-Component-Type Regulators Requires a Small RNA Molecule. Molecular Microbiology, 39, 392-406. [Google Scholar] [CrossRef] [PubMed]
[53] 冼培凤, 等. 蜂毒对胶原诱导性关节炎炎性痛大鼠背根神经节TrkA、TRPV1的影响[J]. 南方医科大学学报, 2016, 36(6): 838-841.
[54] 高海娜, 等. 亮氨酸或组氨酸通过哺乳动物雷帕霉素靶蛋白信号通路影响奶牛乳腺上皮细胞中酪蛋白的合成[J]. 动物营养学报, 2015, 27(4): 1124-1134.
[55] 王珊珊, 等. 组氨酸对体外培养奶牛乳腺上皮细胞β-酪蛋白及酪氨酸激酶2-信号转导与转录激活子5/哺乳动物雷帕霉素靶蛋白信号通路相关磷酸化蛋白表达的影响[J]. 动物营养学报, 2016, 28(3): 916-925.
[56] Brown, J.R. and Auger, K.R. (2011) Phylogenomics of Phosphoinositide Lipid Kinases: Perspectives on the Evolution of Second Messenger Signaling and Drug Discovery. BMC Evolutionary Biology, 11, 4. [Google Scholar] [CrossRef] [PubMed]
[57] Rincon, E., et al. (2012) Diacylglycerol Kinase Zeta: At the Cross-roads of Lipid Signaling and Protein Complex Organization. Progress in Lipid Research, 51, 1-10. [Google Scholar] [CrossRef] [PubMed]
[58] Vivanco, I. and Sawyers, C.L. (2002) The Phosphatidylinositol 3-Kinase AKT Pathway in Human Cancer. Nature Reviews Cancer, 2, 489-501. [Google Scholar] [CrossRef] [PubMed]
[59] Kapeller, R. and Cantley, L.C. (1994) Phosphatidylinositol 3-Kinase. Bioessays, 16, 565-576. [Google Scholar] [CrossRef] [PubMed]
[60] 范军胜, 等. 外周神经损伤的高频超声诊断研究[J]. 中华显微外科杂志, 2003(4): 30-32.
[61] 韩滨, 董敏, 李正翔. 施万细胞在修复外周神经损伤中作用机制的研究进展[J]. 国际神经病学神经外科学杂志, 2021, 48(3): 289-293.
[62] 何新泽, 等. 周围神经损伤的修复:理论研究与技术应用[J]. 中国组织工程研究, 2016, 20(7): 1044-1050.
[63] 李峰, 等. 外周神经损伤的显微外科修复[J]. 中华显微外科杂志, 2004(1): 27-29.
[64] Sunderland, S. (1951) A Classification of Peripheral Nerve Injuries Producing Loss of Function. Brain, 74, 491-516. [Google Scholar] [CrossRef] [PubMed]
[65] Yi, S., et al. (2017) Microarray and qPCR Analyses of Wallerian De-generation in Rat Sciatic Nerves. Frontiers in Cellular Neuroscience, 11, 22. [Google Scholar] [CrossRef] [PubMed]
[66] Gordon, T. and English, A.W. (2016) Strategies to Promote Periph-eral Nerve Regeneration: Electrical Stimulation and/or Exercise. European Journal of Neuroscience, 43, 336-350. [Google Scholar] [CrossRef] [PubMed]
[67] Yi, S., et al. (2019) Tau Modulates Schwann Cell Proliferation, Migration and Differentiation Following Peripheral Nerve Injury. Journal of Cell Science, 132, jcs222059. [Google Scholar] [CrossRef] [PubMed]
[68] 胡琳娜, 等. 电针治疗周围神经损伤的修复机制[J]. 中国组织工程研究与临床康复, 2010, 14(46): 8662-8664.
[69] 李新春, 等. 兔坐骨神经急性挤压伤的MRI与病理学对比初步研究[J]. 中华放射学杂志, 2004(2): 21-26.
[70] Yi, S., et al. (2020) Application of Stem Cells in Peripheral Nerve Re-generation. Burns & Trauma, 8, tkaa002.
[71] Liu, Y., et al. (2019) Tissue-Engineered Nerve Grafts Using a Scaf-fold-Independent and Injectable Drug Delivery System: A Novel Design with Translational Advantages. Journal of Neural Engineering, 16, Article ID: 036030. [Google Scholar] [CrossRef] [PubMed]
[72] Yi, S., et al. (2015) Deep Sequencing and Bioinformatic Analysis of Lesioned Sciatic Nerves after Crush Injury. PLoS ONE, 10, e0143491. [Google Scholar] [CrossRef] [PubMed]
[73] Liao, C., et al. (2016) Tissue-Engineered Conduit Promotes Sci-atic Nerve Regeneration Following Radiation-Induced Injury as Monitored by Magnetic Resonance Imaging. Magnetic Resonance Imaging, 34, 515-523. [Google Scholar] [CrossRef] [PubMed]
[74] Chang, W., et al. (2018) Tissue-Engineered Spiral Nerve Guidance Conduit for Peripheral Nerve Regeneration. Acta Biomaterialia, 73, 302-311. [Google Scholar] [CrossRef] [PubMed]
[75] 陈涛, 等. 高频超声对医源性周围神经损伤的诊断价值[J]. 中国超声医学杂志, 2015, 31(6): 527-529.
[76] 李文伟. 中西医综合治疗医源性周围神经损伤14例报告[J]. 中医正骨, 2006(1): 33-34.
[77] Zhao, J., et al. (2020) Dose-Effect Relationship and Molecular Mechanism by Which BMSC-Derived Exosomes Promote Peripheral Nerve Regeneration after Crush Injury. Stem Cell Research & Therapy, 11, 360. [Google Scholar] [CrossRef] [PubMed]
[78] Nocera, G. and Jacob, C. (2020) Mechanisms of Schwann Cell Plasticity Involved in Peripheral Nerve Repair after Injury. Cellular and Molecular Life Sciences, 77, 3977-3989. [Google Scholar] [CrossRef] [PubMed]
[79] Perkins, N.M. and Tracey, D.J. (2000) Hyperalgesia due to Nerve Injury: Role of Neutrophils. Neuroscience, 101, 745-757. [Google Scholar] [CrossRef
[80] Mueller, M., et al. (2003) Macrophage Response to Periph-eral Nerve Injury: The Quantitative Contribution of Resident and Hematogenous Macrophages. Laboratory Investigation, 83, 175-185. [Google Scholar] [CrossRef
[81] Zigmond, R.E. and Echevarria, F.D. (2019) Macro-phage Biology in the Peripheral Nervous System after Injury. Progress in Neurobiology, 173, 102-121. [Google Scholar] [CrossRef] [PubMed]
[82] Jessen, K.R. and Mirsky, R. (2016) The Repair Schwann Cell and Its Function in Regenerating Nerves. The Journal of Physiology, 594, 3521-3531. [Google Scholar] [CrossRef
[83] Renthal, W., et al. (2020) Transcriptional Reprogramming of Distinct Pe-ripheral Sensory Neuron Subtypes after Axonal Injury. Neuron, 108, 128-144.e9. [Google Scholar] [CrossRef] [PubMed]
[84] 张倩. 研究中枢神经系统损伤后轴突再生和功能恢复的治疗策略[D]: [博士学位论文]. 西安: 第四军医大学, 2017.
[85] 陈威克, 赵国栋, 孔令胜. 自噬在脊髓损伤中的作用及研究进展[J]. 中国医师进修杂志, 2020, 43(9): 851-854.
[86] 周凯亮, 等. 细胞自噬在脊髓损伤中作用的研究进展[J]. 中国骨伤, 2015, 28(8): 695-698.
[87] 黄海城. 自噬促进坐骨神经损伤模型大鼠外周神经再生与运动功能恢复[D]: [硕士学位论文]. 广州: 南方医科大学, 2015.
[88] 李欢, 等. 生长分化因子11对高糖诱导MIN6细胞损伤的保护作用及机制研究[J]. 中华糖尿病杂志, 2017, 9(7): 450-456.
[89] Wen, W., et al. (2020) Mesence-phalic Astrocyte-Derived Neurotrophic Factor (MANF) Regulates Neurite Outgrowth through the Activation of Akt/mTOR and Erk/mTOR Signaling Pathways. Frontiers in Molecular Neuroscience, 13, Article ID: 560020. [Google Scholar] [CrossRef] [PubMed]
[90] Yu, X.Y., et al. (2020) Apatinib Induces Apoptosis and Autoph-agy via the PI3K/AKT/mTOR and MAPK/ERK Signaling Pathways in Neuroblastoma. Oncology Letters, 20, 52.
[91] 刘郁东, 等. 雷帕霉素对不同肿瘤细胞Bax/Bcl-2和活性caspase-3表达的影响[J]. 肿瘤, 2013, 33(2): 138-143+163.
[92] 袁燕, 等. mTOR信号通路在镉诱导PC12细胞凋亡和Bcl-2、Bax蛋白表达中的作用[J]. 中国兽医学报, 2017, 37(1): 107-111.
[93] Gao, L., et al. (2020) 6-Phosphofructo-2-kinase/fructose-2,6-bisphosphatase Suppresses Neuronal Apoptosis by Increasing Glycolysis and Cyclin-Dependent Kinase 1-Mediated Phosphorylation of p27 after Traumatic Spinal Cord Injury in Rats. Cell Transplantation, 29, 1-14. [Google Scholar] [CrossRef] [PubMed]
[94] 巴方, 陈学云, 刘洪亮. 白藜芦醇通过影响细胞外信号调节蛋白激酶信号通路对创伤性脑损伤后的神经保护作用[J]. 中国医科大学学报, 2019, 48(5): 402-405.
[95] 欧阳云, 等. 活络效灵丹通过激活磷脂酰肌醇3激酶/蛋白激酶B信号通路降低青光眼兔视神经损伤的研究[J]. 河北中医, 2020, 42(5): 737-744+801.