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ISSN 1001-5256 (Print)
ISSN 2097-3497 (Online)
CN 22-1108/R
Volume 37 Issue 8
Aug.  2021
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Article Navigation >  Journal of Clinical Hepatology  > 2021  >  37(8): 1970-1974

Mechanism of action of spleen tyrosine kinase in liver diseases

DOI: 10.3969/j.issn.1001-5256.2021.08.049
  • 1.

    Graduate School of Guangxi University of Chinese Medicine, Nanning 530222, China

  • 2.

    Division I of Liver Disease, The First Affiliated Hospital of Guangxi University of Chinese Medicine, Nanning 530023, China

Research funding:

General Project of National Natural Science Foundation of China (81774236);

National Natural Science Foundation of China (81960841);

Natural Science Foundation of Guangxi Province (2018GXNSFAA281096);

Guangxi Science and Technology Program Project - Guangxi Science and Technology Base and Talent Special Project (GK AD17129001)

  • Received Date: 2020-12-29
  • Accepted Date: 2021-01-18
  • Published Date: 2021-08-20
    Abstract
  • Spleen tyrosine kinase (Syk) is a non-receptor tyrosine kinase expressed in most hematopoietic and non-hematopoietic cells and plays an important role in both immune and non-immune biological responses. Syk mediates a variety of cellular responses through immunoreceptor tyrosine-based activation motifs (ITAM)-dependent and ITAM-semi-dependent signaling pathways. Studies have shown that Syk is expressed in liver parenchymal cells and nonparenchymal cells and is closely associated with the pathogenesis, prevention, and treatment of various liver diseases such as liver fibrosis, viral hepatitis, alcoholic liver disease, nonalcoholic steatohepatitis, and hepatocellular carcinoma. This article summarizes the feature and regulatory mechanism of Syk in chronic liver diseases, in order to provide ideas and basis for the treatment of liver diseases.

     

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  • [1]
    LOWELL CA. Src-family and Syk kinases in activating and inhibitory pathways in innate immune cells: Signaling cross talk[J]. Cold Spring Harb Perspect Biol, 2011, 3(3): a002352. DOI: 10.1101/cshperspect.a002352.
    [2]
    PAMUK ON, TSOKOS GC. Spleen tyrosine kinase inhibition in the treatment of autoimmune, allergic and autoinflammatory diseases[J]. Arthritis Res Ther, 2010, 12(6): 222. DOI: 10.1186/ar3198.
    [3]
    SCHWEIGHOFFER E, NYS J, VANES L, et al. TLR4 signals in B lymphocytes are transduced via the B cell antigen receptor and SYK[J]. J Exp Med, 2017, 214(5): 1269-1280. DOI: 10.1084/jem.20161117.
    [4]
    KELLER B, STUMPF I, STROHMEIER V, et al. High SYK expression drives constitutive activation of CD21 low B cells[J]. J Immunol, 2017, 198(11): 4285-4292. DOI: 10.4049/jimmunol.1700079.
    [5]
    YANAGI S, INATOME R, TAKANO T, et al. Syk expression and novel function in a wide variety of tissues[J]. Biochem Biophys Res Commun, 2001, 288(3): 495-498. DOI: 10.1006/bbrc.2001.5788.
    [6]
    QU C, ZHENG D, LI S, et al. Tyrosine kinase SYK is a potential therapeutic target for liver fibrosis[J]. Hepatology, 2018, 68(3): 1125-1139. DOI: 10.1002/hep.29881.
    [7]
    ZHANG Y, OH H, BURTON RA, et al. Tyr130 phosphorylation triggers Syk release from antigen receptor by long-distance conformational uncoupling[J]. Proc Natl Acad Sci U S A, 2008, 105(33): 11760-11765. DOI: 10.1073/pnas.0708583105.
    [8]
    SADA K, TAKANO T, YANAGI S, et al. Structure and function of Syk protein-tyrosine kinase[J]. J Biochem, 2001, 130(2): 177-186. DOI: 10.1093/oxfordjournals.jbchem.a002970.
    [9]
    SLOMIANY BL, SLOMIANY A. Syk: A new target for attenuation of Helicobacter pylori-induced gastric mucosal inflammatory responses[J]. Inflammopharmacology, 2019, 27(2): 203-211. DOI: 10.1007/s10787-019-00577-6.
    [10]
    PAROLA M, PINZANI M. Liver fibrosis: Pathophysiology, pathogenetic targets and clinical issues[J]. Mol Aspects Med, 2019, 65: 37-55. DOI: 10.1016/j.mam.2018.09.002.
    [11]
    NORDSTRÖM A, BERGMAN J, BJÖRK S, et al. A multiple risk factor program is associated with decreased risk of cardiovascular disease in 70-year-olds: A cohort study from Sweden[J]. PLoS Med, 2020, 17(6): e1003135. DOI: 10.1371/journal.pmed.1003135.
    [12]
    CIGROVSKI BERKOVIC M, VIROVIC-JUKIC L, BILIC-CURCIC I, et al. Post-transplant diabetes mellitus and preexisting liver disease - a bidirectional relationship affecting treatment and management[J]. World J Gastroenterol, 2020, 26(21): 2740-2757. DOI: 10.3748/wjg.v26.i21.2740.
    [13]
    GIESECK RL 3rd, WILSON MS, WYNN TA. Type 2 immunity in tissue repair and fibrosis[J]. Nat Rev Immunol, 2018, 18(1): 62-76. DOI: 10.1038/nri.2017.90.
    [14]
    TSUCHIDA T, FRIEDMAN SL. Mechanisms of hepatic stellate cell activation[J]. Nat Rev Gastroenterol Hepatol, 2017, 14(7): 397-411. DOI: 10.1038/nrgastro.2017.38.
    [15]
    NISHIKAWA K, OSAWA Y, KIMURA K. Wnt/β-catenin signaling as a potential target for the treatment of liver cirrhosis using antifibrotic drugs[J]. Int J Mol Sci, 2018, 19(10): 3103. DOI: 10.3390/ijms19103103.
    [16]
    KISSELEVA T. The origin of fibrogenic myofibroblasts in fibrotic liver[J]. Hepatology, 2017, 65(3): 1039-1043. DOI: 10.1002/hep.28948.
    [17]
    MANN J, MANN DA. Transcriptional regulation of hepatic stellate cells[J]. Adv Drug Deliv Rev, 2009, 61(7-8): 497-512. DOI: 10.1016/j.addr.2009.03.011.
    [18]
    AOUAR B, KOVAROVA D, LETARD S, et al. Dual role of the tyrosine kinase syk in regulation of Toll-like receptor signaling in plasmacytoid dendritic cells[J]. PLoS One, 2016, 11(6): e0156063. DOI: 10.1371/journal.pone.0156063.
    [19]
    ZEKRI AR, HAFEZ MM, BAHNASSY AA, et al. Genetic profile of Egyptian hepatocellular-carcinoma associated with hepatitis C virus Genotype 4 by 15 K cDNA microarray: Preliminary study[J]. BMC Res Notes, 2008, 1: 106. DOI: 10.1186/1756-0500-1-106.
    [20]
    BUKONG TN, KODYS K, SZABO G. Human ezrin-moesin-radixin proteins modulate hepatitis C virus infection[J]. Hepatology, 2013, 58(5): 1569-1579. DOI: 10.1002/hep.26500.
    [21]
    XUE Y, MARS WM, BOWEN W, et al. Hepatitis C virus mimics effects of glypican-3 on CD81 and promotes development of hepatocellular carcinomas via activation of hippo pathway in hepatocytes[J]. Am J Pathol, 2018, 188(6): 1469-1477. DOI: 10.1016/j.ajpath.2018.02.013.
    [22]
    BUKONG TN, KODYS K, SZABO G. A novel human radixin peptide inhibits hepatitis C virus infection at the level of cell entry[J]. Int J Pept Res Ther, 2014, 20(3): 269-276. DOI: 10.1007/s10989-013-9390-8.
    [23]
    INUBUSHI S, NAGANO-FUJⅡ M, KITAYAMA K, et al. Hepatitis C virus NS5A protein interacts with and negatively regulates the non-receptor protein tyrosine kinase Syk[J]. J Gen Virol, 2008, 89(Pt 5): 1231-1242. DOI: 10.1099/vir.0.83510-0.
    [24]
    GBD 2016 Alcohol Collaborators. Alcohol use and burden for 195 countries and territories, 1990-2016: A systematic analysis for the Global Burden of Disease Study 2016[J]. Lancet, 2018, 392(10152): 1015-1035. DOI: 10.1016/S0140-6736(18)31310-2.
    [25]
    DUNN W, SHAH VH. Pathogenesis of alcoholic liver disease[J]. Clin Liver Dis, 2016, 20(3): 445-456. DOI: 10.1016/j.cld.2016.02.004.
    [26]
    STICKEL F, DATZ C, HAMPE J, et al. Pathophysiology and management of alcoholic liver disease: Update 2016[J]. Gut Liver, 2017, 11(2): 173-188. DOI: 10.5009/gnl16477.
    [27]
    PETRASEK J, IRACHETA-VELLVE A, CSAK T, et al. STING-IRF3 pathway links endoplasmic reticulum stress with hepatocyte apoptosis in early alcoholic liver disease[J]. Proc Natl Acad Sci U S A, 2013, 110(41): 16544-16549. DOI: 10.1073/pnas.1308331110.
    [28]
    GUO J, FRIEDMAN SL. Toll-like receptor 4 signaling in liver injury and hepatic fibrogenesis[J]. Fibrogenesis Tissue Repair, 2010, 3: 21. DOI: 10.1186/1755-1536-3-21.
    [29]
    SZABO G. Gut-liver axis in alcoholic liver disease[J]. Gastroenterology, 2015, 148(1): 30-36. DOI: 10.1053/j.gastro.2014.10.042.
    [30]
    ROH YS, SEKI E. Toll-like receptors in alcoholic liver disease, non-alcoholic steatohepatitis and carcinogenesis[J]. J Gastroenterol Hepatol, 2013, 28(Suppl 1): 38-42. DOI: 10.1111/jgh.12019.
    [31]
    ZHOU H, YU M, ZHAO J, et al. IRAKM-Mincle axis links cell death to inflammation: Pathophysiological implications for chronic alcoholic liver disease[J]. Hepatology, 2016, 64(6): 1978-1993. DOI: 10.1002/hep.28811.
    [32]
    KURNIAWAN DW, JAJORIYA AK, DHAWAN G, et al. Therapeutic inhibition of spleen tyrosine kinase in inflammatory macrophages using PLGA nanoparticles for the treatment of non-alcoholic steatohepatitis[J]. J Control Release, 2018, 288: 227-238. DOI: 10.1016/j.jconrel.2018.09.004.
    [33]
    BUKONG TN, IRACHETA-VELLVE A, SAHA B, et al. Inhibition of spleen tyrosine kinase activation ameliorates inflammation, cell death, and steatosis in alcoholic liver disease[J]. Hepatology, 2016, 64(4): 1057-1071. DOI: 10.1002/hep.28680.
    [34]
    BUKONG TN, IRACHETA-VELLVE A, GYONGYOSI B, et al. Therapeutic benefits of spleen tyrosine kinase inhibitor administration on binge drinking-induced alcoholic liver injury, steatosis, and inflammation in mice[J]. Alcohol Clin Exp Res, 2016, 40(7): 1524-1530. DOI: 10.1111/acer.13096.
    [35]
    FRIEDMAN SL, NEUSCHWANDER-TETRI BA, RINELLA M, et al. Mechanisms of NAFLD development and therapeutic strategies[J]. Nat Med, 2018, 24(7): 908-922. DOI: 10.1038/s41591-018-0104-9.
    [36]
    YOUNOSSI ZM, KOENIG AB, ABDELATIF D, et al. Global epidemiology of nonalcoholic fatty liver disease-Meta-analytic assessment of prevalence, incidence, and outcomes[J]. Hepatology, 2016, 64(1): 73-84. DOI: 10.1002/hep.28431.
    [37]
    FANG YL, CHEN H, WANG CL, et al. Pathogenesis of non-alcoholic fatty liver disease in children and adolescence: From "two hit theory" to "multiple hit model"[J]. World J Gastroenterol, 2018, 24(27): 2974-2983. DOI: 10.3748/wjg.v24.i27.2974.
    [38]
    BIEGHS V, TRAUTWEIN C. Innate immune signaling and gut-liver interactions in non-alcoholic fatty liver disease[J]. Hepatobiliary Surg Nutr, 2014, 3(6): 377-385. DOI: 10.3978/j.issn.2304-3881.2014.12.04.
    [39]
    KIZILTAS S. Toll-like receptors in pathophysiology of liver diseases[J]. World J Hepatol, 2016, 8(32): 1354-1369. DOI: 10.4254/wjh.v8.i32.1354.
    [40]
    CARPINO G, NOBILI V, RENZI A, et al. Macrophage activation in pediatric nonalcoholic fatty liver disease (NAFLD) correlates with hepatic progenitor cell response via Wnt3a pathway[J]. PLoS One, 2016, 11(6): e0157246. DOI: 10.1371/journal.pone.0157246.
    [41]
    FLYNN R, ALLEN JL, LUZNIK L, et al. Targeting Syk-activated B cells in murine and human chronic graft-versus-host disease[J]. Blood, 2015, 125(26): 4085-4094. DOI: 10.1182/blood-2014-08-595470.
    [42]
    MALIK AF, HOQUE R, OUYANG X, et al. Inflammasome components Asc and caspase-1 mediate biomaterial-induced inflammation and foreign body response[J]. Proc Natl Acad Sci U S A, 2011, 108(50): 20095-20100. DOI: 10.1073/pnas.1105152108.
    [43]
    MRIDHA AR, WREE A, ROBERTSON A, et al. NLRP3 inflammasome blockade reduces liver inflammation and fibrosis in experimental NASH in mice[J]. J Hepatol, 2017, 66(5): 1037-1046. DOI: 10.1016/j.jhep.2017.01.022.
    [44]
    SONG IJ, YANG YM, INOKUCHI-SHIMIZU S, et al. The contribution of toll-like receptor signaling to the development of liver fibrosis and cancer in hepatocyte-specific TAK1-deleted mice[J]. Int J Cancer, 2018, 142(1): 81-91. DOI: 10.1002/ijc.31029.
    [45]
    YUAN Y, WANG J, LI J, et al. Frequent epigenetic inactivation of spleen tyrosine kinase gene in human hepatocellular carcinoma[J]. Clin Cancer Res, 2006, 12(22): 6687-6695. DOI: 10.1158/1078-0432.CCR-06-0921.
    [46]
    SHIN SH, LEE KH, KIM BH, et al. Downregulation of spleen tyrosine kinase in hepatocellular carcinoma by promoter CpG island hypermethylation and its potential role in carcinogenesis[J]. Lab Invest, 2014, 94(12): 1396-1405. DOI: 10.1038/labinvest.2014.118.
    [47]
    CARONE C, OLIVANI A, DALLA VALLE R, et al. Immune gene expression profile in hepatocellular carcinoma and surrounding tissue predicts time to tumor recurrence[J]. Liver Cancer, 2018, 7(3): 277-294. DOI: 10.1159/000486764.
    [48]
    HONG J, HU K, YUAN Y, et al. CHK1 targets spleen tyrosine kinase (L) for proteolysis in hepatocellular carcinoma[J]. J Clin Invest, 2012, 122(6): 2165-2175. DOI: 10.1172/JCI61380.
    [49]
    HONG J, YUAN Y, WANG J, et al. Expression of variant isoforms of the tyrosine kinase SYK determines the prognosis of hepatocellular carcinoma[J]. Cancer Res, 2014, 74(6): 1845-1856. DOI: 10.1158/0008-5472.CAN-13-2104.
    [50]
    TORRES-HERNANDEZ A, WANG W, NIKIFOROV Y, et al. Targeting SYK signaling in myeloid cells protects against liver fibrosis and hepatocarcinogenesis[J]. Oncogene, 2019, 38(23): 4512-4526. DOI: 10.1038/s41388-019-0734-5.
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