血小板的研究现状及其影响肝再生的机制
The Mechanism and Research Progress of Platelet Affecting Liver Regeneration
DOI: 10.12677/HJBM.2023.132028, PDF,   
作者: 王 鹏, 丁 隆:佳木斯大学附属第一医院普外二科,黑龙江 佳木斯;杨 宇:佳木斯大学基础医学院,黑龙江 佳木斯
关键词: 肝再生血小板炎症反应组织修复肿瘤Liver Regeneration Platelet Inflammatory Reaction Tissue Repair Tumor
摘要: 肝脏是体内重要的代谢器官,具有损伤后独特的再生能力。系统而全面的理解肝脏再生的机制才能找到相应有效的治疗方法。血小板除了在止血以及血栓形成方面发挥作用,同时能够参与炎症反应、肿瘤、组织修复等病理生理事件。近年来的研究结果提示血小板在肝再生中具有重要作用。本文就血小板上述作用以及血小板影响肝再生的作用机制及其研究进展作一综述,希望为相关领域的探索提供基础研究。
Abstract: The liver is an important metabolic organ in the body and has unique regenerative capacity after injury. A systematic and comprehensive understanding of the mechanism of liver regeneration can lead to effective treatment. Platelets not only play a role in hemostasis and thrombosis, but also participate in pathophysiological events such as inflammatory response, tumor and tissue repair. Recent studies suggest that platelets play an important role in liver regeneration. This article reviews the above effects of platelets and the mechanism and research progress of platelets affecting liver regeneration, hoping to provide basic research for the exploration of related fields.
文章引用:王鹏, 杨宇, 丁隆. 血小板的研究现状及其影响肝再生的机制[J]. 生物医学, 2023, 13(2): 246-254. https://doi.org/10.12677/HJBM.2023.132028

参考文献

[1] Ocak, İ., Topaloğlu, S. and Acarli, K. (2020) Posthepatectomy Liver Failure. Turkish Journal of Medical Sciences, 50, 1491-1503. [Google Scholar] [CrossRef] [PubMed]
[2] Fausto, N. and Campbell, J.S. (2003) The Role of Hepatocytes and Oval Cells in Liver Regeneration and Repopulation. Mechanisms of Development, 120, 117-130. [Google Scholar] [CrossRef
[3] Popper, H., Kent, G. and Stein, R. (1957) Ductular Cell Reaction in the Liver in Hepatic Injury. Journal of the Mount Sinai Hospital, New York, 24, 551-556.
[4] Factor, V.M., Radaeva, S.A. and Thorgeirsson, S.S. (1994) Origin and Fate of Oval Cells in Dipin-Induced Hepatocarcinogenesis in the Mouse. The American Journal of Pathology, 145, 409-422.
[5] Evarts, R.P., Nagy, P., Marsden, E., et al. (1987) A Precursor-Product Relationship Exists between Oval Cells and Hepatocytes in Rat Liver. Carcinogenesis, 8, 1737-1740. [Google Scholar] [CrossRef] [PubMed]
[6] Lázaro, C.A., Rhim, J.A., Yamada, Y., et al. (1998) Generation of Hepatocytes from Oval Cell Precursors in Culture. Cancer Research, 58, 5514-5522.
[7] Lowes, K.N., Brennan, B.A., Yeoh, G.C., et al. (1999) Oval Cell Numbers in Human Chronic Liver Diseases Are Directly Related to Disease Severity. The American Journal of Pathology, 154, 537-541. [Google Scholar] [CrossRef
[8] Wang, B., Zhao, L., Fish, M., et al. (2015) Self-Renewing Diploid Axin2(+) Cells Fuel Homeostatic Renewal of the Liver. Nature, 524, 180-185. [Google Scholar] [CrossRef] [PubMed]
[9] Pu, W., Zhang, H., Huang, X., et al. (2016) Mfsd2a+ Hepatocytes Repopulate the Liver during Injury and Regeneration. Nature Communications, 7, 13369. [Google Scholar] [CrossRef] [PubMed]
[10] Schaub, J.R., Huppert, K.A., Kurial, S.N.T., et al. (2018) De Novo Formation of the Biliary System by TGFβ-Medi- ated Hepatocyte Transdifferentiation. Nature, 557, 247-251. [Google Scholar] [CrossRef] [PubMed]
[11] Li, D., Li, W. and Hui, L. (2016) Hybrid Hepatocyte: A Newly Identified Player for Regeneration in Hepatic Injuries. Hepatology, 64, 2244-2246. [Google Scholar] [CrossRef] [PubMed]
[12] Font-Burgada, J., Shalapour, S., Ramaswamy, S., et al. (2015) Hybrid Periportal Hepatocytes Regenerate the Injured Liver without Giving Rise to Cancer. Cell, 162, 766-779. [Google Scholar] [CrossRef] [PubMed]
[13] Lin, S., Nascimento, E.M., Gajera, C.R., et al. (2018) Distributed Hepatocytes Expressing Telomerase Repopulate the Liver in Homeostasis and Injury. Nature, 556, 244-248. [Google Scholar] [CrossRef] [PubMed]
[14] Deng, X., Zhang, X., Li, W., et al. (2018) Chronic Liver Injury Induces Conversion of Biliary Epithelial Cells into Hepatocytes. Cell Stem Cell, 23, 114-122.e3. [Google Scholar] [CrossRef] [PubMed]
[15] Ding, B.S., Nolan, D.J., Butler, J.M., et al. (2010) Inductive Angiocrine Signals from Sinusoidal Endothelium Are Required for Liver Regeneration. Nature, 468, 310-315. [Google Scholar] [CrossRef] [PubMed]
[16] Maher, J.J. (1993) Cell-Specific Expression of Hepatocyte Growth Factor in Liver. Upregulation in Sinusoidal Endothelial Cells after Carbon Tetrachloride. Journal of Clinical Investigation, 91, 2244-2252. [Google Scholar] [CrossRef
[17] Lecouter, J., Moritz, D.R., Li, B., et al. (2003) Angiogenesis-Independent Endothelial Protection of Liver: Role of VEGFR-1. Science, 299, 890-893. [Google Scholar] [CrossRef] [PubMed]
[18] Greene, A.K., Wiener, S., Puder, M., et al. (2003) Endothelial-Directed Hepatic Regeneration after Partial Hepatectomy. Annals of Surgery, 237, 530-535. [Google Scholar] [CrossRef
[19] Nanji, A.A., Tahan, S.R., Wei, Y., et al. (1994) Hepatic Sinusoidal Endothelial Cell G1/S Arrest Correlates with Severity of Alcoholic Liver Injury in the Rat. Gastroenterology, 107, 818-823. [Google Scholar] [CrossRef] [PubMed]
[20] Taniguchi, E., Sakisaka, S., Matsuo, K., et al. (2001) Expression and Role of Vascular Endothelial Growth Factor in Liver Regeneration after Partial Hepatectomy in Rats. Journal of Histochemistry & Cytochemistry, 49, 121-130. [Google Scholar] [CrossRef] [PubMed]
[21] Friedman, S.L. (2003) Liver Fibrosis—From Bench to Bedside. Journal of Hepatology, 38, S38-S53. [Google Scholar] [CrossRef
[22] Higashi, T., Friedman, S.L. and Hoshida, Y. (2017) Hepatic Stellate Cells as Key Target in Liver Fibrosis. Advanced Drug Delivery Reviews, 121, 27-42. [Google Scholar] [CrossRef] [PubMed]
[23] Dropmann, A., Dediulia, T., Breitkopf-Heinlein, K., et al. (2016) TGF-β1 and TGF-β2 Abundance in Liver Diseases of Mice and Men. Oncotarget, 7, 19499-19518. [Google Scholar] [CrossRef] [PubMed]
[24] Michalopoulos, G.K. and Bhushan, B. (2021) Liver Regeneration: Biological and Pathological Mechanisms and Implications. Nature Reviews Gastroenterology & Hepatology, 18, 40-55. [Google Scholar] [CrossRef] [PubMed]
[25] Deangelis, R.A., Kovalovich, K., Cressman, D.E., et al. (2001) Normal Liver Regeneration in p50/Nuclear Factor KappaB1 Knockout Mice. Hepatology, 33, 915-924. [Google Scholar] [CrossRef] [PubMed]
[26] Streetz, K.L., Luedde, T., Manns, M.P., et al. (2000) Interleukin 6 and Liver Regeneration. Gut, 47, 309-312. [Google Scholar] [CrossRef] [PubMed]
[27] 曾宪飞, 胡兴斌. 血小板诱导肝再生的研究进展[J]. 中国输血杂志, 2018, 31(10): 1205-1208.
[28] Murata, S., Maruyama, T., Nowatari, T., et al. (2014) Signal Transduction of Platelet-Induced Liver Regeneration and Decrease of Liver Fibrosis. International Journal of Molecular Sciences, 15, 5412-5425. [Google Scholar] [CrossRef] [PubMed]
[29] Xiang, B., Zhang, G., Guo, L., et al. (2013) Platelets Protect from Septic Shock by Inhibiting Macrophage-Dependent Inflammation via the Cyclooxygenase 1 Signalling Pathway. Nature Communications, 4, 2657. [Google Scholar] [CrossRef] [PubMed]
[30] Iannacone, M. (2016) Platelet-Mediated Modulation of Adaptive Immunity. Seminars in Immunology, 28, 555-560. [Google Scholar] [CrossRef] [PubMed]
[31] Tsukiji, N., Inoue, O., Morimoto, M., et al. (2018) Platelets Play an Essential Role in Murine Lung Development through Clec-2/Podoplanin Interaction. Blood, 132, 1167-1179. [Google Scholar] [CrossRef] [PubMed]
[32] Cognasse, F., Hamzeh, H., Chavarin, P., et al. (2005) Evidence of Toll-Like Receptor Molecules on Human Platelets. Immunology & Cell Biology, 83, 196-198. [Google Scholar] [CrossRef] [PubMed]
[33] Semple, J.W., Italiano, J.E. and Freedman, J. (2011) Platelets and the Immune Continuum. Nature Reviews Immunology, 11, 264-274. [Google Scholar] [CrossRef] [PubMed]
[34] Kral, J.B., Schrottmaier, W.C., Salzmann, M., et al. (2016) Platelet Interaction with Innate Immune Cells. Transfusion Medicine and Hemotherapy, 43, 78-88. [Google Scholar] [CrossRef] [PubMed]
[35] Harrison, P. and Cramer, E.M. (1993) Platelet Alpha-Granules. Blood Reviews, 7, 52-62. [Google Scholar] [CrossRef
[36] Mcnicol, A. and Israels, S.J. (1999) Platelet Dense Granules: Structure, Function and Implications for Haemostasis. Thrombosis Research, 95, 1-18. [Google Scholar] [CrossRef
[37] Li, N. (2008) Platelet-Lymphocyte Cross-Talk. Journal of Leukocyte Biology, 83, 1069-1078. [Google Scholar] [CrossRef] [PubMed]
[38] Lesurtel, M. and Clavien, P.A. (2014) Platelet-Derived Serotonin: Translational Implications for Liver Regeneration. Hepatology, 60, 30-33. [Google Scholar] [CrossRef] [PubMed]
[39] Nieswandt, B., Hafner, M., Echtenacher, B., et al. (1999) Lysis of Tumor Cells by Natural Killer Cells in Mice Is Impeded by Platelets. Cancer Research, 59, 1295-1300.
[40] Zucchella, M., Dezza, L., Pacchiarini, L., et al. (1989) Human Tumor Cells Cultured “in Vitro” Activate Platelet Function by Producing ADP or Thrombin. Haematologica, 74, 541-545.
[41] Aitokallio-Tallberg, A., Kärkkäinen, J., Pantzar, P., et al. (1985) Prostacyclin and Thromboxane in Breast Cancer: Relationship between Steroid Receptor Status and Medroxyprogesterone Acetate. British Journal of Cancer, 51, 671-674. [Google Scholar] [CrossRef] [PubMed]
[42] Aitokallio-Tallberg, A.M., Viinikka, L.U. and Ylikorkala, R.O. (1988) Increased Synthesis of Prostacyclin and Thromboxane in Human Ovarian Malignancy. Cancer Research, 48, 2396-2398.
[43] Yu, L.X., Yan, L., Yang, W., et al. (2014) Platelets Promote Tumour Metastasis via Interaction between TLR4 and Tumour Cell-Released High-Mobility Group Box1 Protein. Nature Communications, 5, 5256. [Google Scholar] [CrossRef] [PubMed]
[44] Ward, Y., Lake, R., Faraji, F., et al. (2018) Platelets Promote Metastasis via Binding Tumor CD97 Leading to Bidirectional Signaling that Coordinates Transendothelial Migration. Cell Reports, 23, 808-822. [Google Scholar] [CrossRef] [PubMed]
[45] Han, X., Guo, B., Li, Y., et al. (2014) Tissue Factor in Tumor Microenvironment: A Systematic Review. Journal of Hematology Oncology, 7, 54. [Google Scholar] [CrossRef] [PubMed]
[46] Adams, G.N., Rosenfeldt, L., Frederick, M., et al. (2015) Colon Cancer Growth and Dissemination Relies upon Thrombin, Stromal PAR-1, and Fibrinogen. Cancer Research, 75, 4235-4243. [Google Scholar] [CrossRef
[47] Queiroz, K.C., Shi, K., Duitman, J., et al. (2014) Protease-Activated Receptor-1 Drives Pancreatic Cancer Progression and Chemoresistance. International Journal of Cancer, 135, 2294-2304. [Google Scholar] [CrossRef] [PubMed]
[48] Tsopanoglou, N.E. and Maragoudakis, M.E. (1999) On the Mechanism of Thrombin-Induced Angiogenesis. Potentiation of Vascular Endothelial Growth Factor Activity on Endothelial Cells by Up-Regulation of Its Receptors. Journal of Biological Chemistry, 274, 23969-23976. [Google Scholar] [CrossRef] [PubMed]
[49] Chen, D., Abrahams, J.M., Smith, L.M., et al. (2008) Regenerative Repair after Endoluminal Injury in Mice with Specific Antagonism of Protease Activated Receptors on CD34+ Vascular Progenitors. Blood, 111, 4155-4164. [Google Scholar] [CrossRef] [PubMed]
[50] Konstantoulaki, M., Kouklis, P. and Malik, A.B. (2003) Protein Kinase C Modifications of VE-Cadherin, p120, and Beta-Catenin Contribute to Endothelial Barrier Dysregulation Induced by Thrombin. The American Journal of Physiology-Lung Cellular and Molecular Physiology, 285, L434-L442. [Google Scholar] [CrossRef] [PubMed]
[51] Shao, B., Wahrenbrock, M.G., Yao, L., et al. (2011) Carcinoma Mucins Trigger Reciprocal Activation of Platelets and Neutrophils in a Murine Model of Trousseau Syndrome. Blood, 118, 4015-4023. [Google Scholar] [CrossRef] [PubMed]
[52] Blair, P. and Flaumenhaft, R. (2009) Platelet Alpha-Granules: Basic Biology and Clinical Correlates. Blood Reviews, 23, 177-189. [Google Scholar] [CrossRef] [PubMed]
[53] Neumüller, J., Ellinger, A. and Wagner, T. (2015) Transmission Electron Microscopy of Platelets from Apheresis and Buffy-Coat-Derived Platelet Concentrates. In: Maaz, K., Ed., The Transmission Electron Microscope, IntechOpen, London, 255-284. [Google Scholar] [CrossRef
[54] Crowley, S.T., Dempsey, E.C., Horwitz, K.B., et al. (1994) Platelet-Induced Vascular Smooth Muscle Cell Proliferation Is Modulated by the Growth Amplification Factors Serotonin and Adenosine Diphosphate. Circulation, 90, 1908-1918. [Google Scholar] [CrossRef
[55] Langer, H.F., Stellos, K., Steingen, C., et al. (2009) Platelet Derived bFGF Mediates Vascular Integrative Mechanisms of Mesenchymal Stem Cells in Vitro. Journal of Molecular and Cellular Cardiology, 47, 315-325. [Google Scholar] [CrossRef] [PubMed]
[56] Kanikarla Marie, P., Fowlkes, N.W., Afshar-Kharghan, V., et al. (2021) The Provocative Roles of Platelets in Liver Disease and Cancer. Frontiers in Oncology, 11, Article ID: 643815. [Google Scholar] [CrossRef] [PubMed]
[57] Murata, S., Ohkohchi, N., Matsuo, R., et al. (2007) Platelets Promote Liver Regeneration in Early Period after Hepatectomy in Mice. World Journal of Surgery, 31, 808-816. [Google Scholar] [CrossRef] [PubMed]
[58] Lesurtel, M., Graf, R., Aleil, B., et al. (2006) Platelet-Derived Serotonin Mediates Liver Regeneration. Science, 312, 104-107. [Google Scholar] [CrossRef] [PubMed]
[59] Shimabukuro, R., Kawanaka, H., Tomikawa, M., et al. (2009) Effect of Thrombopoietin on Platelet Counts and Liver Regeneration after Partial Hepatectomy in a Rat Model. Surgery Today, 39, 1054-1059. [Google Scholar] [CrossRef] [PubMed]
[60] Takahashi, K., Kozuma, Y., Suzuki, H., et al. (2013) Human Platelets Promote Liver Regeneration with Kupffer Cells in SCID Mice. Journal of Surgical Research, 180, 62-72. [Google Scholar] [CrossRef] [PubMed]
[61] Matsuo, R., Nakano, Y. and Ohkohchi, N. (2011) Platelet Administration via the Portal Vein Promotes Liver Regeneration in Rats after 70% Hepatectomy. Annals of Surgery, 253, 759-763. [Google Scholar] [CrossRef
[62] Alkozai, E.M., Nijsten, M.W., De Jong, K.P., et al. (2010) Immediate Postoperative Low Platelet Count Is Associated with Delayed Liver Function Recovery after Partial Liver Resection. Annals of Surgery, 251, 300-306. [Google Scholar] [CrossRef
[63] Wang, H.Q., Yang, J., Yang, J.Y., et al. (2014) Low Immediate Postoperative Platelet Count Is Associated with Hepatic Insufficiency after Hepatectomy. World Journal of Gastroenterology, 20, 11871-11877. [Google Scholar] [CrossRef] [PubMed]
[64] Li, L., Wang, H., Yang, J., et al. (2015) Immediate Postoperative Low Platelet Counts after Living Donor Liver Transplantation Predict Early Allograft Dysfunction. Medicine (Baltimore), 94, e1373. [Google Scholar] [CrossRef
[65] Han, S., Park, H.W., Song, J.H., et al. (2016) Association between Intraoperative Platelet Transfusion and Early Graft Regeneration in Living Donor Liver Transplantation. Annals of Surgery, 264, 1065-1072. [Google Scholar] [CrossRef
[66] Nakamura, M., Shibazaki, M., Nitta, Y., et al. (1998) Translocation of Platelets into Disse Spaces and Their Entry into Hepatocytes in Response to Lipopolysaccharides, Interleukin-1 and Tumour Necrosis Factor: The Role of Kupffer Cells. Journal of Hepatology, 28, 991-999. [Google Scholar] [CrossRef
[67] Lang, P.A., Contaldo, C., Georgiev, P., et al. (2008) Aggravation of Viral Hepatitis by Platelet-Derived Serotonin. Nature Medicine, 14, 756-761. [Google Scholar] [CrossRef] [PubMed]
[68] Meyer, J., Lejmi, E., Fontana, P., et al. (2015) A Focus on the Role of Platelets in Liver Regeneration: Do Platelet-Endothelial Cell Interactions Initiate the Regenerative Process? Journal of Hepatology, 63, 1263-1271. [Google Scholar] [CrossRef] [PubMed]
[69] Li, J., Van Der Wal, D.E., Zhu, G., et al. (2015) Desialylation Is a Mechanism of Fc-Independent Platelet Clearance and a Therapeutic Target in Immune Thrombocytopenia. Nature Communications, 6, 7737. [Google Scholar] [CrossRef] [PubMed]
[70] Rumjantseva, V., Grewal, P.K., Wandall, H.H., et al. (2009) Dual Roles for Hepatic Lectin Receptors in the Clearance of Chilled Platelets. Nature Medicine, 15, 1273-1280. [Google Scholar] [CrossRef] [PubMed]
[71] Grozovsky, R., Begonja, A.J., Liu, K., et al. (2015) The Ashwell-Morell Receptor Regulates Hepatic Thrombopoietin Production via JAK2-STAT3 Signaling. Nature Medicine, 21, 47-54. [Google Scholar] [CrossRef] [PubMed]
[72] Kirschbaum, M., Karimian, G., Adelmeijer, J., et al. (2015) Horizontal RNA Transfer Mediates Platelet-Induced Hepatocyte Proliferation. Blood, 126, 798-806. [Google Scholar] [CrossRef] [PubMed]
[73] Starlinger, P., Haegele, S., Offensperger, F., et al. (2016) The Profile of Platelet α-Granule Released Molecules Affects Postoperative Liver Regeneration. Hepatology, 63, 1675-1688. [Google Scholar] [CrossRef] [PubMed]
[74] Kondo, R., Yano, H., Nakashima, O., et al. (2013) Accumulation of Platelets in the Liver May Be an Important Contributory Factor to Thrombocytopenia and Liver Fibrosis in Chronic Hepatitis C. Journal of Gastroenterology, 48, 526-534. [Google Scholar] [CrossRef] [PubMed]
[75] Bockhorn, M., Goralski, M., Prokofiev, D., et al. (2007) VEGF Is Important for Early Liver Regeneration after Partial Hepatectomy. Journal of Surgical Research, 138, 291-299. [Google Scholar] [CrossRef] [PubMed]
[76] Meyer, J., Balaphas, A., Fontana, P., et al. (2020) Platelet Interactions with Liver Sinusoidal Endothelial Cells and Hepatic Stellate Cells Lead to Hepatocyte Proliferation. Cells, 9, 1243. [Google Scholar] [CrossRef] [PubMed]
[77] Murata, S., Matsuo, R., Ikeda, O., et al. (2008) Platelets Promote Liver Regeneration under Conditions of Kupffer Cell Depletion after Hepatectomy in Mice. World Journal of Surgery, 32, 1088-1096. [Google Scholar] [CrossRef] [PubMed]
[78] Abshagen, K., Eipel, C., Kalff, J.C., et al. (2007) Loss of NF-kappaB Activation in Kupffer Cell-Depleted Mice Impairs Liver Regeneration after Partial Hepatectomy. The American Journal of Physiology-Gastrointestinal and Liver Physiology, 292, G1570-G1577. [Google Scholar] [CrossRef] [PubMed]
[79] Takahashi, K., Murata, S. and Ohkohchi, N. (2013) Novel Therapy for Liver Regeneration by Increasing the Number of Platelets. Surgery Today, 43, 1081-1087. [Google Scholar] [CrossRef] [PubMed]
[80] López, M.L., Uribe-Cruz, C., Osvaldt, A., et al. (2016) Encapsulated Platelets Modulate Kupffer Cell Activation and Reduce Oxidative Stress in a Model of Acute Liver Failure. Liver Transplantation, 22, 1562-1572. [Google Scholar] [CrossRef] [PubMed]