中文｜English
ISSN 1001-5256 (Print)
ISSN 2097-3497 (Online)
CN 22-1108/R
Volume 38 Issue 9
Sep.  2022
Turn off MathJax
Article Contents
Article Navigation >  Journal of Clinical Hepatology  > 2022  >  38(9): 2177-2181

Role of lipocalin-2 in the development and progression of liver diseases

DOI: 10.3969/j.issn.1001-5256.2022.09.044

  • Jiangsu Key Laboratory for New Drug Screening, Institute of Pharmaceutical Research, China Pharmaceutical University, Nanjing 210009, China

Research funding:

National Natural Science Foundation of China (81773766)

More Information
  • Corresponding author: YUAN Shengtao, yuanst1967@163.com (ORCID: 0000-0002-5626-6532)
  • Received Date: 2022-02-18
  • Accepted Date: 2022-03-20
  • Published Date: 2022-09-20
    Abstract
  • Lipocalin-2 (LCN2) is a secreted glycoprotein originally purified from mouse kidney cells infected with simian virus 40 and plays a key role in the control of cellular homeostasis during inflammation and the response to cellular stress or injury, and it is considered a potential biomarker for rheumatic diseases, cancer, liver diseases, and inflammatory diseases. Studies have shown that LCN2 is expressed in hepatic parenchymal and nonparenchymal cells and is secreted into the bloodstream, and it is closely associated with the development and progression of acute liver injury, liver cirrhosis, viral hepatitis, alcoholic liver disease, nonalcoholic fatty liver disease, and hepatocellular carcinoma. This article summarizes the animal experiments and clinical studies on the association of LCN2 with the pathogenesis of liver diseases, in order to provide new ideas and therapeutic targets for the prevention and treatment of liver diseases.

     

    • FullText(HTML)
  • loading
    • References(44)
  • [1]
    MUSSAP M, DEGRANDI R, FRAVEGA M, et al. Acute kidney injury in critically ill infants: the role of urine Neutrophil Gelatinase-Associated Lipocalin (NGAL)[J]. J Matern Fetal Neonatal Med, 2010, 23(Suppl 3): 70-72. DOI: 10.3109/14767058.2010.508217.
    [2]
    KUNZENDORF U, HAASE M, RÖLVER L, et al. Novel aspects of pharmacological therapies for acute renal failure[J]. Drugs, 2010, 70(9): 1099-1114. DOI: 10.2165/11535890-000000000-00000.
    [3]
    BOLIGNANO D, COPPOLINO G, DONATO V, et al. Neutrophil gelatinase-associated lipocalin (NGAL): a new piece of the anemia puzzle?[J]. Med Sci Monit, 2010, 16(6): RA131-RA135. http://www.researchgate.net/profile/Giuseppe_Coppolino/publication/44639284_Neutrophil_gelatinase-associated_lipocalin_(NGAL)_a_new_piece_of_the_anemia_puzzle/links/0fcfd509cdf2262bcb000000
    [4]
    BOLIGNANO D, DONATO V, LACQUANITI A, et al. Neutrophil gelatinase-associated lipocalin (NGAL) in human neoplasias: a new protein enters the scene[J]. Cancer Lett, 2010, 288(1): 10-16. DOI: 10.1016/j.canlet.2009.05.027.
    [5]
    CHAKRABORTY S, KAUR S, GUHA S, et al. The multifaceted roles of neutrophil gelatinase associated lipocalin (NGAL) in inflammation and cancer[J]. Biochim Biophys Acta, 2012, 1826(1): 129-169. DOI: 10.1016/j.bbcan.2012.03.008.
    [6]
    TRIEBEL S, BLÄSER J, REINKE H, et al. A 25 kDa alpha 2-microglobulin-related protein is a component of the 125 kDa form of human gelatinase[J]. FEBS Lett, 1992, 314(3): 386-388. DOI: 10.1016/0014-5793(92)81511-j.
    [7]
    FLOWER DR, NORTH AC, SANSOM CE. The lipocalin protein family: structural and sequence overview[J]. Biochim Biophys Acta, 2000, 1482(1-2): 9-24. DOI: 10.1016/s0167-4838(00)00148-5.
    [8]
    KJELDSEN L, JOHNSEN AH, SENGELØV H, et al. Isolation and primary structure of NGAL, a novel protein associated with human neutrophil gelatinase[J]. J Biol Chem, 1993, 268(14): 10425-10432.
    [9]
    AXELSSON L, BERGENFELDT M, OHLSSON K. Studies of the release and turnover of a human neutrophil lipocalin[J]. Scand J Clin Lab Invest, 1995, 55(7): 577-588. DOI: 10.3109/00365519509110257.
    [10]
    KRIZANAC M, MASS SANCHEZ PB, WEISKIRCHEN R, et al. A scoping review on lipocalin-2 and its role in non-alcoholic steatohepatitis and hepatocellular carcinoma[J]. Int J Mol Sci, 2021, 22(6): 2865. DOI: 10.3390/ijms22062865.
    [11]
    GOETZ DH, HOLMES MA, BORREGAARD N, et al. The neutrophil lipocalin NGAL is a bacteriostatic agent that interferes with siderophore-mediated iron acquisition[J]. Mol Cell, 2002, 10(5): 1033-1043. DOI: 10.1016/s1097-2765(02)00708-6.
    [12]
    KOYNER JL, PARIKH CR. Clinical utility of biomarkers of AKI in cardiac surgery and critical illness[J]. Clin J Am Soc Nephrol, 2013, 8(6): 1034-1042. DOI: 10.2215/CJN.05150512.
    [13]
    CHIEN MH, YING TH, YANG SF, et al. Lipocalin-2 induces apoptosis in human hepatocellular carcinoma cells through activation of mitochondria pathways[J]. Cell Biochem Biophys, 2012, 64(3): 177-186. DOI: 10.1007/s12013-012-9370-1.
    [14]
    ASIMAKOPOULOU A, BORKHAM-KAMPHORST E, HENNING M, et al. Lipocalin-2 (LCN2) regulates PLIN5 expression and intracellular lipid droplet formation in the liver[J]. Biochim Biophys Acta, 2014, 1842(10): 1513-1524. DOI: 10.1016/j.bbalip.2014.07.017.
    [15]
    CHUNG IH, CHEN CY, LIN YH, et al. Thyroid hormone-mediated regulation of lipocalin 2 through the Met/FAK pathway in liver cancer[J]. Oncotarget, 2015, 6(17): 15050-15064. DOI: 10.18632/oncotarget.3670.
    [16]
    WANG YP, YU GR, LEE MJ, et al. Lipocalin-2 negatively modulates the epithelial-to-mesenchymal transition in hepatocellular carcinoma through the epidermal growth factor (TGF-beta1)/Lcn2/Twist1 pathway[J]. Hepatology, 2013, 58(4): 1349-1361. DOI: 10.1002/hep.26467.
    [17]
    XIE Y, LI J, QIN H, et al. Paramylon from Euglena gracilis prevents lipopolysaccharide-induced acute liver injury[J]. Front Immunol, 2022, 12: 797096. DOI: 10.3389/fimmu.2021.797096.
    [18]
    BORKHAM-KAMPHORST E, DREWS F, WEISKIRCHEN R. Induction of lipocalin-2 expression in acute and chronic experimental liver injury moderated by pro-inflammatory cytokines interleukin-1β through nuclear factor-κB activation[J]. Liver Int, 2011, 31(5): 656-665. DOI: 10.1111/j.1478-3231.2011.02495.x.
    [19]
    LABBUS K, HENNING M, BORKHAM-KAMPHORST E, et al. Proteomic profiling in Lipocalin 2 deficient mice under normal and inflammatory conditions[J]. J Proteomics, 2013, 78: 188-196. DOI: 10.1016/j.jprot.2012.11.021.
    [20]
    BORKHAM-KAMPHORST E, van de LEUR E, ZIMMERMANN HW, et al. Protective effects of lipocalin-2 (LCN2) in acute liver injury suggest a novel function in liver homeostasis[J]. Biochim Biophys Acta, 2013, 1832(5): 660-673. DOI: 10.1016/j.bbadis.2013.01.014.
    [21]
    POWELL EE, WONG VW, RINELLA M. Non-alcoholic fatty liver disease[J]. Lancet, 2021, 397(10290): 2212-2224. DOI: 10.1016/S0140-6736(20)32511-3.
    [22]
    LAW IK, XU A, LAM KS, et al. Lipocalin-2 deficiency attenuates insulin resistance associated with aging and obesity[J]. Diabetes, 2010, 59(4): 872-882. DOI: 10.2337/db09-1541.
    [23]
    AUGUET T, TERRA X, QUINTERO Y, et al. Liver lipocalin 2 expression in severely obese women with non alcoholic fatty liver disease[J]. Exp Clin Endocrinol Diabete, 2013, 121(2): 119-124. DOI: 10.1055/s-0032-1331696.
    [24]
    LU J, LIN L, YE C, et al. Serum NGAL is superior to cystatin C in predicting the prognosis of acute-on-chronic liver failure[J]. Ann Hepatol, 2019, 18(1): 155-164. DOI: 10.5604/01.3001.0012.7907.
    [25]
    MILNER KL, van der POORTEN D, XU A, et al. Adipocyte fatty acid binding protein levels relate to inflammation and fibrosis in nonalcoholic fatty liver disease[J]. Hepatology, 2009, 49(6): 1926-1934. DOI: 10.1002/hep.22896.
    [26]
    XU Y, ZHU Y, JADHAV K, et al. Lipocalin-2 protects against diet-induced nonalcoholic fatty liver disease by targeting hepatocytes[J]. Hepatol Commun, 2019, 3(6): 763-775. DOI: 10.1002/hep4.1341.
    [27]
    SEMBA T, NISHIMURA M, NISHIMURA S, et al. The FLS (fatty liver Shionogi) mouse reveals local expressions of lipocalin-2, CXCL1 and CXCL9 in the liver with non-alcoholic steatohepatitis[J]. BMC Gastroenterol, 2013, 13: 120. DOI: 10.1186/1471-230X-13-120.
    [28]
    ASIMAKOPOULOU A, BORKHAM-KAMPHORST E, TACKE F, et al. Lipocalin-2 (NGAL/LCN2), a "help-me" signal in organ inflammation[J]. Hepatology, 2016, 63(2): 669-671. DOI: 10.1002/hep.27930.
    [29]
    YE D, YANG K, ZANG S, et al. Lipocalin-2 mediates non-alcoholic steatohepatitis by promoting neutrophil-macrophage crosstalk via the induction of CXCR2[J]. J Hepatol, 2016, 65(5): 988-997. DOI: 10.1016/j.jhep.2016.05.041.
    [30]
    KIM HG, HUANG M, XIN Y, et al. The epigenetic regulator SIRT6 protects the liver from alcohol-induced tissue injury by reducing oxidative stress in mice[J]. J Hepatol, 2019, 71(5): 960-969. DOI: 10.1016/j.jhep.2019.06.019.
    [31]
    WIESER V, TYMOSZUK P, ADOLPH TE, et al. Lipocalin 2 drives neutrophilic inflammation in alcoholic liver disease[J]. J Hepatol, 2016, 64(4): 872-880. DOI: 10.1016/j.jhep.2015.11.037.
    [32]
    ZHANG Y, LONG X, RUAN X, et al. SIRT2-mediated deacetylation and deubiquitination of C/EBPβ prevents ethanol-induced liver injury[J]. Cell Discov, 2021, 7(1): 93. DOI: 10.1038/s41421-021-00326-6.
    [33]
    BATALLER R, BRENNER DA. Liver fibrosis[J]. J Clin Invest, 2005, 115(2): 209-218. DOI: 10.1172/JCI24282.
    [34]
    ARIZA X, GRAUPERA I, COLL M, et al. Neutrophil gelatinase-associated lipocalin is a biomarker of acute-on-chronic liver failure and prognosis in cirrhosis[J]. J Hepatol, 2016, 65(1): 57-65. DOI: 10.1016/j.jhep.2016.03.002.
    [35]
    KIM JW, LEE SH, JEONG SH, et al. Increased urinary lipocalin-2 reflects matrix metalloproteinase-9 activity in chronic hepatitis C with hepatic fibrosis[J]. Tohoku J Exp Med, 2010, 222(4): 319-327. DOI: 10.1620/tjem.222.319.
    [36]
    CHEN J, ARGEMI J, ODENA G, et al. Hepatic lipocalin 2 promotes liver fibrosis and portal hypertension[J]. Sci Rep, 2020, 10(1): 15558. DOI: 10.1038/s41598-020-72172-7.
    [37]
    SUNG H, FERLAY J, SIEGEL RL, et al. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries[J]. CA Cancer J Clin, 2021, 71(3): 209-249. DOI: 10.3322/caac.21660.
    [38]
    CANDIDO S, MAESTRO R, POLESEL J, et al. Roles of neutrophil gelatinase-associated lipocalin (NGAL) in human cancer[J]. Oncotarget, 2014, 5(6): 1576-1594. DOI: 10.18632/oncotarget.1738.
    [39]
    BARSOUM I, ELGOHARY MN, BASSIONY MAA. Lipocalin-2: A novel diagnostic marker for hepatocellular carcinoma[J]. Cancer Biomark, 2020, 28(4): 523-528. DOI: 10.3233/CBM-190084.
    [40]
    ABDELSAMEEA E, NADA A, OMAR N, et al. Urine neutrophil gelatinase-associated lipocalin a possible diagnostic marker for egyptian hepatocellular carcinoma patients[J]. Asian Pac J Cancer Prev, 2020, 21(8): 2259-2264. DOI: 10.31557/APJCP.2020.21.8.2259.
    [41]
    ZHANG Y, FAN Y, MEI Z. NGAL and NGALR overexpression in human hepatocellular carcinoma toward a molecular prognostic classification[J]. Cancer Epidemiol, 2012, 36(5): e294-e299. DOI: 10.1016/j.canep.2012.05.012.
    [42]
    DERTLI R, BIYIK M, YOLACAN R, et al. May neutrophil gelatinase-associated lipocalin (NGAL) level predict mortality in patients with hepatocellular carcinoma (HCC)?[J]. J Gastrointest Cancer, 2020, 51(3): 932-938. DOI: 10.1007/s12029-019-00323-9.
    [43]
    YAO F, DENG Y, ZHAO Y, et al. A targetable LIFR-NF-κB-LCN2 axis controls liver tumorigenesis and vulnerability to ferroptosis[J]. Nat Commun, 2021, 12(1): 7333. DOI: 10.1038/s41467-021-27452-9.
    [44]
    LEE EK, KIM HJ, LEE KJ, et al. Inhibition of the proliferation and invasion of hepatocellular carcinoma cells by lipocalin 2 through blockade of JNK and PI3K/Akt signaling[J]. Int J Oncol, 2011, 38(2): 325-333. DOI: 10.3892/ijo.2010.854.
    • Relative Articles
    • Supplements(0)
    • Cited By
  • 加载中

Catalog

    通讯作者: 陈斌, bchen63@163.com
    • 1. 

      沈阳化工大学材料科学与工程学院 沈阳 110142

    1. 本站搜索
    2. 百度学术搜索
    3. 万方数据库搜索
    4. CNKI搜索
    Get Citation
    PDF
    XML

    Article Metrics

    Article views (478) PDF downloads(69) Cited by()
    Proportional views
    Related
        

    The first journal specializing in hepatobiliary and pancreatic diseases in China

    Supervisor：Ministry of Education of the People's Republic of China

    Sponsor：Jilin University

    Academic Support: Chinese Society of Hepatology，Chinese Medical Association

    Address: 461 Xinjiang Road, Changchun

    Submit：0431-88782044

    Peer review：0431-88783542

    Email：lcgdb@vip.163.com

    About Journal

    Submission Guideline

    Journal Online

    Hepatobiliary College

    Guidelines

    YesterdayIP[]YesterdayPV[]TodayIP[]TodayPV[]Online[]

    Website Design © 2020 Editorial Board of Journal of Clinical Hepatology 吉ICP备10000617号-1 Supported by: Beijing Renhe Information Technology Co. Ltd  

    /

    DownLoad:  Full-Size Img  PowerPoint
    Return
    Return