中文English
ISSN 1001-5256 (Print)
ISSN 2097-3497 (Online)
CN 22-1108/R

留言板

尊敬的读者、作者、审稿人, 关于本刊的投稿、审稿、编辑和出版的任何问题, 您可以本页添加留言。我们将尽快给您答复。谢谢您的支持!

姓名
邮箱
手机号码
标题
留言内容
验证码

肝内胆管改变与肝纤维化的关系

尤文铮 任万雷 宣世英 胡豆豆

引用本文:
Citation:

肝内胆管改变与肝纤维化的关系

DOI: 10.3969/j.issn.1001-5256.2022.01.032
基金项目: 

国家自然科学基金青年科学基金项目 (81800543)

利益冲突声明:所有作者均声明不存在利益冲突。
作者贡献声明:尤文铮负责撰写修改论文; 任万雷负责参与文献的收集、整理; 宣世英、胡豆豆负责拟定写作思路,指导撰写文章并最后定稿。
详细信息
    通信作者:

    宣世英,xuansydxy@163.com

    胡豆豆,hudoudou1984@163.com

Association between intrahepatic bile duct alterations and liver fibrosis

Research funding: 

Youth Science Fund Project by National Natural Science Foundation of China (81800543)

  • 摘要: 肝硬化是由多种原因引起的以弥漫性纤维组织增生、肝小叶结构破坏、假小叶形成为特征的肝病。在多种肝硬化动物模型及不同病因肝硬化患者中均可见胆管增生。多种神经肽、神经递质及激素等调节因子参与的信号通路调控胆管增生。增生的胆管通过介导星状细胞增殖、活化,促进肝纤维化的形成。总结了肝硬化时肝内胆管系统的改变及其对纤维化进程的影响,胆管细胞增生与肝纤维化相关的信号通路,以及胆管结构的动态演变对肝纤维化程度的预测价值。提出胆管增生可能成为干预肝纤维化的潜在靶点,为早期治疗及逆转肝纤维化提供新的思路和方法。

     

  • [1] GBD 2017 Cirrhosis Collaborators. The global, regional, and national burden of cirrhosis by cause in 195 countries and territories, 1990-2017: A systematic analysis for the Global Burden of Disease Study 2017[J]. Lancet, 2020, 5(3): 245-266. DOI: 10.1016/S2468-1253(19)30349-8.
    [2] LI H. Angiogenesis in the progression from liver fibrosis to cirrhosis and hepatocelluar carcinoma[J]. Expert Rev Gastroenterol Hepatol, 2021, 15(3): 217-233. DOI: 10.1080/17474124.2021.1842732.
    [3] NGUYEN T, TANG W, NAN L, et al. The role of bile duct reactive change in the pathogenesis of liver fibrosis due to hepatitis C[J]. Exp Mol Pathol, 2005, 79(2): 95-99. DOI: 10.1016/j.yexmp.2005.04.010.
    [4] RICHARDSON MM, JONSSON JR, POWELL EE, et al. Progressive fibrosis in nonalcoholic steatohepatitis: Association with altered regeneration and a ductular reaction[J]. Gastroenterology, 2007, 133(1): 80-90. DOI: 10.1053/j.gastro.2007.05.012.
    [5] RÓKUSZ A, VERES D, SZVCS A, et al. Ductular reaction correlates with fibrogenesis but does not contribute to liver regeneration in experimental fibrosis models[J]. PLoS One, 2017, 12(4): e0176518. DOI: 10.1371/journal.pone.0176518.
    [6] LV WJ, ZHAO XY, HU DD, et al. Insight into bile duct reaction to obstruction from a three-dimensional perspective using ex vivo phase-contrast CT[J]. Radiology, 2021, 299(3): 597-610. DOI: 10.1148/radiol.2021203967.
    [7] SVEGLIATI-BARONI G, FARACI G, FABRIS L, et al. Insulin resistance and necroinflammation drives ductular reaction and epithelial-mesenchymal transition in chronic hepatitis C[J]. Gut, 2011, 60(1): 108-115. DOI: 10.1136/gut.2010.219741.
    [8] WOOD MJ, GADD VL, POWELL LW, et al. Ductular reaction in hereditary hemochromatosis: The link between hepatocyte senescence and fibrosis progression[J]. Hepatology, 2014, 59(3): 848-857. DOI: 10.1002/hep.26706.
    [9] QIN L, ZHAO X, JIAN J, et al. High-resolution 3D visualization of ductular proliferation of bile duct ligation-induced liver fibrosis in rats using X-ray phase contrast computed tomography[J]. Sci Rep, 2017, 7(1): 4215. DOI: 10.1038/s41598-017-03993-2.
    [10] MILANI S, HERBST H, SCHUPPAN D, et al. Procollagen expression by nonparenchymal rat liver cells in experimental biliary fibrosis[J]. Gastroenterology, 1990, 98(1): 175-184. DOI: 10.1016/0016-5085(90)91307-r.
    [11] CLOUSTON AD, POWELL EE, WALSH MJ, et al. Fibrosis correlates with a ductular reaction in hepatitis C: Roles of impaired replication, progenitor cells and steatosis[J]. Hepatology, 2005, 41(4): 809-818. DOI: 10.1002/hep.20650.
    [12] GOUW AS, CLOUSTON AD, THEISE ND. Ductular reactions in human liver: Diversity at the interface[J]. Hepatology, 2011, 54(5): 1853-1863. DOI: 10.1002/hep.24613.
    [13] HUBEL E, SAROHA A, PARK WJ, et al. Sortilin deficiency reduces ductular reaction, hepatocyte apoptosis, and liver fibrosis in cholestatic-induced liver injury[J]. Am J Pathol, 2017, 187(1): 122-133. DOI: 10.1016/j.ajpath.2016.09.005.
    [14] HALL C, SATO K, WU N, et al. Regulators of cholangiocyte proliferation[J]. Gene Expr, 2017, 17(2): 155-171. DOI: 10.3727/105221616X692568.
    [15] FABRIS L, BRIVIO S, CADAMURO M, et al. Revisiting epithelial-to-mesenchymal transition in liver fibrosis: Clues for a better understanding of the "reactive" biliary epithelial phenotype[J]. Stem Cells Int, 2016, 2016: 2953727. DOI: 10.1155/2016/2953727.
    [16] MASYUK TV, RITMAN EL, LARUSSO NF. Hepatic artery and portal vein remodeling in rat liver: Vascular response to selective cholangiocyte proliferation[J]. Am J Pathol, 2003, 162(4): 1175-1182. DOI: 10.1016/S0002-9440(10)63913-2.
    [17] MCMILLIN M, DEMORROW S, GLASER S, et al. Melatonin inhibits hypothalamic gonadotropin-releasing hormone release and reduces biliary hyperplasia and fibrosis in cholestatic rats[J]. Am J Physiol Gastrointest Liver Physiol, 2017, 313(5): G410-G418. DOI: 10.1152/ajpgi.00421.2016.
    [18] SATO K, MENG F, GIANG T, et al. Mechanisms of cholangiocyte responses to injury[J]. Biochim Biophys Acta Mol Basis Dis, 2018, 1864(4 Pt B): 1262-1269. DOI: 10.1016/j.bbadis.2017.06.017.
    [19] GLASER SS, GAUDIO E, MILLER T, et al. Cholangiocyte proliferation and liver fibrosis[J]. Expert Rev Mol Med, 2009, 11: e7. DOI: 10.1017/S1462399409000994.
    [20] POLAK JM, COULLING I, BLOOM S, et al. Immunofluorescent localization of secretin and enteroglucagon in human intestinal mucosa[J]. Scand J Gastroenterol, 1971, 6(8): 739-744. DOI: 10.3109/00365527109179946.
    [21] ALPINI G, ROBERTS S, KUNTZ SM, et al. Morphological, molecular, and functional heterogeneity of cholangiocytes from normal rat liver[J]. Gastroenterology, 1996, 110(5): 1636-1643. DOI: 10.1053/gast.1996.v110.pm8613073.
    [22] GLASER S, LAM IP, FRANCHITTO A, et al. Knockout of secretin receptor reduces large cholangiocyte hyperplasia in mice with extrahepatic cholestasis induced by bile duct ligation[J]. Hepatology, 2010, 52(1): 204-214. DOI: 10.1002/hep.23657.
    [23] GLASER S, MENG F, HAN Y, et al. Secretin stimulates biliary cell proliferation by regulating expression of microRNA 125b and microRNA let7a in mice[J]. Gastroenterology, 2014, 146(7): 1795-1808. e12. DOI: 10.1053/j.gastro.2014.02.030.
    [24] WU N, MENG F, INVERNIZZI P, et al. The secretin/secretin receptor axis modulates liver fibrosis through changes in transforming growth factor-β1 biliary secretion in mice[J]. Hepatology, 2016, 64(3): 865-879. DOI: 10.1002/hep.28622.
    [25] GUERRIER M, ATTILI F, ALPINI G, et al. Prolonged administration of secretin to normal rats increases biliary proliferation and secretin-induced ductal secretory activity[J]. Hepatobiliary Surg Nutr, 2014, 3(3): 118-125. DOI: 10.3978/j.issn.2304-3881.2014.04.04.
    [26] KENNEDY L, FRANCIS H, INVERNIZZI P, et al. Secretin/secretin receptor signaling mediates biliary damage and liver fibrosis in early-stage primary biliary cholangitis[J]. FASEB J, 2019, 33(9): 10269-10279. DOI: 10.1096/fj.201802606R.
    [27] NISHIO T, HU R, KOYAMA Y, et al. Activated hepatic stellate cells and portal fibroblasts contribute to cholestatic liver fibrosis in MDR2 knockout mice[J]. J Hepatol, 2019, 71(3): 573-585. DOI: 10.1016/j.jhep.2019.04.012.
    [28] SPITSIN S, PAPPA V, DOUGLAS SD. Truncation of neurokinin-1 receptor-Negative regulation of substance P signaling[J]. J Leukoc Biol, 2018, 103(6): 1043-1051. DOI: 10.1002/JLB.3MIR0817-348R.
    [29] CECI L, FRANCIS H, ZHOU T, et al. Knockout of the tachykinin receptor 1 in the Mdr2-/- (Abcb4-/-) mouse model of primary sclerosing cholangitis reduces biliary damage and liver fibrosis[J]. Am J Pathol, 2020, 190(11): 2251-2266. DOI: 10.1016/j.ajpath.2020.07.007.
    [30] GLASER S, GAUDIO E, RENZI A, et al. Knockout of the neurokinin-1 receptor reduces cholangiocyte proliferation in bile duct-ligated mice[J]. Am J Physiol Gastrointest Liver Physiol, 2011, 301(2): G297-G305. DOI: 10.1152/ajpgi.00418.2010.
    [31] WAN Y, MENG F, WU N, et al. Substance P increases liver fibrosis by differential changes in senescence of cholangiocytes and hepatic stellate cells[J]. Hepatology, 2017, 66(2): 528-541. DOI: 10.1002/hep.29138.
    [32] TATEMOTO K, HOSOYA M, HABATA Y, et al. Isolation and characterization of a novel endogenous peptide ligand for the human APJ receptor[J]. Biochem Biophys Res Commun, 1998, 251(2): 471-476. DOI: 10.1006/bbrc.1998.9489.
    [33] HOSOYA M, KAWAMATA Y, FUKUSUMI S, et al. Molecular and functional characteristics of APJ. Tissue distribution of mRNA and interaction with the endogenous ligand apelin[J]. J Biol Chem, 2000, 275(28): 21061-21067. DOI: 10.1074/jbc.M908417199.
    [34] MELGAR-LESMES P, PERRAMON M, JIMÉNEZ W. Roles of the hepatic endocannabinoid and apelin systems in the pathogenesis of liver fibrosis[J]. Cells, 2019, 8(11): 1311. DOI: 10.3390/cells8111311.
    [35] PRINCIPE A, MELGAR-LESMES P, FERNÁNDEZ-VARO G, et al. The hepatic apelin system: A new therapeutic target for liver disease[J]. Hepatology, 2008, 48(4): 1193-1201. DOI: 10.1002/hep.22467.
    [36] REICHENBACH V, ROS J, FERNÁNDEZ-VARO G, et al. Prevention of fibrosis progression in CCl4-treated rats: Role of the hepatic endocannabinoid and apelin systems[J]. J Pharmacol Exp Ther, 2012, 340(3): 629-637. DOI: 10.1124/jpet.111.188078.
    [37] CHEN L, ZHOU T, WHITE T, et al. The apelin-apelin receptor axis triggers cholangiocyte proliferation and liver fibrosis during mouse models of cholestasis[J]. Hepatology, 2021, 73(6): 2411-2428. DOI: 10.1002/hep.31545.
  • 加载中
计量
  • 文章访问数:  528
  • HTML全文浏览量:  101
  • PDF下载量:  80
  • 被引次数: 0
出版历程
  • 收稿日期:  2021-05-18
  • 录用日期:  2021-06-11
  • 出版日期:  2022-01-20
  • 分享
  • 用微信扫码二维码

    分享至好友和朋友圈

目录

    /

    返回文章
    返回