中文English
ISSN 1001-5256
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

肝细胞极性调控

毛元鹏 魏红山

引用本文:
Citation:

肝细胞极性调控

DOI: 10.3969/j.issn.1001-5256.2022.11.043
基金项目: 

北京市医院管理中心消化内科学科协同发展中心专项 XXZ0404;

北京市自然科学基金 7202071;

国家自然科学基金 82170541

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:毛元鹏负责拟定写作思路,资料分析,撰写论文;魏红山负责课题设计,指导撰写论文并最终定稿。
详细信息
    通信作者:

    魏红山,drwei@ccmu.edu.cn

Regulation of hepatocyte polarity

Research funding: 

The Digestive Medical Coordinated Development Center of Beijing Municipal Administration of Hospitals XXZ0404;

Natural Science Foundation of Beijing 7202071;

National Natural Science Foundation of China 82170541

More Information
  • 摘要: 肝细胞是高度极化的细胞。肝细胞极性的建立和维持对肝细胞的诸多功能至关重要。肝细胞极性的动态稳定与诸多因素相关,包括细胞间连接、极性蛋白复合体以及多个信号通路。当极性受到破坏,肝细胞功能往往出现异常,最终可能导致各类肝脏疾病的发生。目前,关于肝细胞极性调控相关研究仍然较少,多种关键因素尚未得到完全阐明。本文简要介绍了近年来肝细胞极性调控相关研究进展。

     

  • 表  1  肝细胞极性紊乱所致胆汁淤积性肝病相关蛋白质/基因

    Table  1.   Proteins/genes associated with cholestatic liver diseases caused by disorder of hepatocyte polarity

    编码基因 蛋白质主要功能 相关疾病 相关报道
    TJP2 TJ构成 家族性高胆碱血症 Carlton(2003)
    CLDN1 TJ构成 新生儿鱼鳞病硬化性胆管炎综合征 Hadj-Rabia(2004)
    ATP8B1 磷脂翻转酶 进行性家族性肝内胆汁淤积症 Bull(1998)
    ABCB4 磷脂输出泵 进行性家族性肝内胆汁淤积症 Deleuze(1996)
    ABCB11 胆汁盐输出泵 进行性家族性肝内胆汁淤积症 Strautnieks(1998)
    ABCC2 小管有机阴离子转运 肝内和阻塞性胆汁淤积 Trauner(1997)
    VPS33B 囊泡细胞内转运和蛋白质相互作用 关节挛缩-肾功能障碍-胆汁淤积综合征 Gissen(2004)
    MYO5B 小管形成;促进ABC转运蛋白正常运输 进行性家族性肝内胆汁淤积症 Girard(2014)
    下载: 导出CSV
  • [1] RUST K, WODARZ A. Transcriptional control of apical-basal polarity regulators[J]. Int J Mol Sci, 2021, 22(22): 12340. DOI: 10.3390/ijms222212340.
    [2] BUNTING CH, EADES CC. The effect of mechanical tension upon the polarity of growing fibroblasts[J]. J Exp Med, 1926, 44(2): 147-149. DOI: 10.1084/jem.44.2.147.
    [3] FOMICHEVA M, TROSS EM, MACARA IG. Polarity proteins in oncogenesis[J]. Curr Opin Cell Biol, 2020, 62: 26-30. DOI: 10.1016/j.ceb.2019.07.016.
    [4] WISHER MH, EVANS WH. Functional polarity of the rat hepatocyte surface membrane. Isolation and characterization of plasma-membrane subfractions from the blood-sinusoidal, bile-Canalicular and contiguous surfaces of the hepatocyte[J]. Biochem J, 1975, 146(2): 375-388. DOI: 10.1042/bj1460375.
    [5] TREYER A, MVSCH A. Hepatocyte polarity[J]. Compr Physiol, 2013, 3(1): 243-287. DOI: 10.1002/cphy.c120009.
    [6] OTANI T, FURUSE M. Tight junction structure and function revisited[J]. Trends Cell Biol, 2020, 30(10): 805-817. DOI: 10.1016/j.tcb.2020.08.004.
    [7] TOCAN V, HAYASE J, KAMAKURA S, et al. Hepatocyte polarity establishment and apical lumen formation are organized by Par3, Cdc42, and aPKC in conjunction with Lgl[J]. J Biol Chem, 2021, 297(6): 101354. DOI: 10.1016/j.jbc.2021.101354.
    [8] MENDONSA AM, NA TY, GUMBINER BM. E-cadherin in contact inhibition and cancer[J]. Oncogene, 2018, 37(35): 4769-4780. DOI: 10.1038/s41388-018-0304-2.
    [9] MANOU D, CAON I, BOURIS P, et al. The complex interplay between extracellular matrix and cells in tissues[J]. Methods Mol Biol, 2019, 1952: 1-20. DOI: 10.1007/978-1-4939-9133-4_1.
    [10] FAN X, CHUAN S, HONGSHAN W. Protein O glycosylation regulates activation of hepatic stellate cells[J]. Inflammation, 2013, 36(6): 1248-1252. DOI: 10.1007/s10753-013-9662-7.
    [11] HAO X, GAO M, HE L, et al. Deficiency of O-linked-glycosylation regulates activation of T cells and aggravates Concanavalin A-induced liver injury[J]. Toxicology, 2020, 433-434: 152411. DOI: 10.1016/j.tox.2020.152411.
    [12] ZHANG X, GUO L, ZHANG X, et al. GLT25D2 is critical for inflammatory immune response to promote acetaminophen-induced hepatotoxicity by autophagy pathway[J]. Front Pharmacol, 2020, 11: 01187. DOI: 10.3389/fphar.2020.01187.
    [13] YANG J, HE L, GAO M, et al. Collagen β(1-O) galactosyltransferase 2 deficiency contributes to lipodystrophy and aggravates NAFLD related to HMW adiponectin in mice[J]. Metabolism, 2021, 120: 154777. DOI: 10.1016/j.metabol.2021.154777.
    [14] HE L, YE X, GAO M, et al. Down-regulation of GLT25D1 inhibited collagen secretion and involved in liver fibrogenesis[J]. Gene, 2020, 729: 144233. DOI: 10.1016/j.gene.2019.144233.
    [15] FU D, WAKABAYASHI Y, IDO Y, et al. Regulation of bile canalicular network formation and maintenance by AMP-activated protein kinase and LKB1[J]. J Cell Sci, 2010, 123(Pt 19): 3294-3302. DOI: 10.1242/jcs.068098.
    [16] KAPIL S, SHARMA BK, PATIL M, et al. The cell polarity protein Scrib functions as a tumor suppressor in liver cancer[J]. Oncotarget, 2017, 8(16): 26515-26531. DOI: 10.18632/oncotarget.15713.
    [17] WAN S, MEYER AS, WEILER S, et al. Cytoplasmic localization of the cell polarity factor scribble supports liver tumor formation and tumor cell invasiveness[J]. Hepatology, 2018, 67(5): 1842-1856. DOI: 10.1002/hep.29669.
    [18] MÉDINA E, WILLIAMS J, KLIPFELL E, et al. Crumbs interacts with moesin and beta(Heavy)-spectrin in the apical membrane skeleton of Drosophila[J]. J Cell Biol, 2002, 158(5): 941-951. DOI: 10.1083/jcb.200203080.
    [19] SOTILLOS S, DÍAZ-MECO MT, CAMINERO E, et al. DaPKC-dependent phosphorylation of Crumbs is required for epithelial cell polarity in Drosophila[J]. J Cell Biol, 2004, 166(4): 549-557. DOI: 10.1083/jcb.200311031.ew
    [20] JUNG HY, FATTET L, TSAI JH, et al. Apical-basal polarity inhibits epithelial-mesenchymal transition and tumour metastasis by PAR-complex-mediated SNAI1 degradation[J]. Nat Cell Biol, 2019, 21(3): 359-371. DOI: 10.1038/s41556-019-0291-8.
    [21] WANG S, CAI J, ZHANG S, et al. Loss of polarity protein Par3, via transcription factor Snail, promotes bladder cancer metastasis[J]. Cancer Sci, 2021, 112(7): 2625-2641. DOI: 10.1111/cas.14920.
    [22] JIA Z, CHENG Y, JIANG X, et al. 3D Culture system for liver tissue mimicking hepatic plates for improvement of human hepatocyte (C3A) function and polarity[J]. Biomed Res Int, 2020, 2020: 6354183. DOI: 10.1155/2020/6354183.
    [23] DAO THI VL, WU X, BELOTE RL, et al. Stem cell-derived polarized hepatocytes[J]. Nat Commun, 2020, 11(1): 1677. DOI: 10.1038/s41467-020-15337-2.
    [24] BLAU BJ, MIKI T. The role of cellular interactions in the induction of hepatocyte polarity and functional maturation in stem cell-derived hepatic cells[J]. Differentiation, 2019, 106: 42-48. DOI: 10.1016/j.diff.2019.02.006.
    [25] GISSEN P, ARIAS IM. Structural and functional hepatocyte polarity and liver disease[J]. J Hepatol, 2015, 63(4): 1023-1037. DOI: 10.1016/j.jhep.2015.06.015.
    [26] NG KH, LE GOASCOGNE C, AMBORADE E, et al. Reversible induction of rat hepatoma cell polarity with bile acids[J]. J Cell Sci, 2000, 113 Pt 23: 4241-4251. DOI: 10.1242/jcs.113.23.4241.
    [27] FU D, WAKABAYASHI Y, LIPPINCOTT-SCHWARTZ J, et al. Bile acid stimulates hepatocyte polarization through a cAMP-Epac-MEK-LKB1-AMPK pathway[J]. Proc Natl Acad Sci U S A, 2011, 108(4): 1403-1408. DOI: 10.1073/pnas.1018376108.
    [28] KANG S, FU D. Bioenergetics for hepatocyte polarization: Coordination of multiple cellular organelles and the master regulator AMPK[J]. Crit Rev Eukaryot Gene Expr, 2019, 29(5): 483-497. DOI: 10.1615/CritRevEukaryotGeneExpr.2019029911.
    [29] WICKLINE ED, AWUAH PK, BEHARI J, et al. Hepatocyte γ-catenin compensates for conditionally deleted β-catenin at adherens junctions[J]. J Hepatol, 2011, 55(6): 1256-1262. DOI: 10.1016/j.jhep.2011.03.014.
    [30] PRADHAN-SUNDD T, LIU S, SINGH S, et al. Dual β-catenin and γ-catenin loss in hepatocytes impacts their polarity through altered transforming growth factor-β and hepatocyte nuclear factor 4α signaling[J]. Am J Pathol, 2021, 191(5): 885-901. DOI: 10.1016/j.ajpath.2021.02.008.
    [31] KAMIYA A, GONZALEZ FJ. TNF-alpha regulates mouse fetal hepatic maturation induced by oncostatin M and extracellular matrices[J]. Hepatology, 2004, 40(3): 527-536. DOI: 10.1002/hep.20362.
    [32] di MAIRA G, FOGLIA B, NAPIONE L, et al. Oncostatin M is overexpressed in NASH-related hepatocellular carcinoma and promotes cancer cell invasiveness and angiogenesis[J]. J Pathol, 2022, 257(1): 82-95. DOI: 10.1002/path.5871.
    [33] YEH MM, BOSCH DE, DAOUD SS. Role of hepatocyte nuclear factor 4-alpha in gastrointestinal and liver diseases[J]. World J Gastroenterol, 2019, 25(30): 4074-4091. DOI: 10.3748/wjg.v25.i30.4074.
    [34] THYMIAKOU E, OTHMAN A, HORNEMANN T, et al. Defects in High Density Lipoprotein metabolism and hepatic steatosis in mice with liver-specific ablation of Hepatocyte Nuclear Factor 4A[J]. Metabolism, 2020, 110: 154307. DOI: 10.1016/j.metabol.2020.154307.
    [35] LV DD, ZHOU LY, TANG H. Hepatocyte nuclear factor 4α and cancer-related cell signaling pathways: a promising insight into cancer treatment[J]. Exp Mol Med, 2021, 53(1): 8-18. DOI: 10.1038/s12276-020-00551-1.
    [36] LV J, KONG Y, GAO Z, et al. LncRNA TUG1 interacting with miR-144 contributes to proliferation, migration and tumorigenesis through activating the JAK2/STAT3 pathway in hepatocellular carcinoma[J]. Int J Biochem Cell Biol, 2018, 101: 19-28. DOI: 10.1016/j.biocel.2018.05.010.
    [37] BELOUZARD S, DANNEELS A, FÉNÉANT L, et al. Entry and release of hepatitis C virus in polarized human hepatocytes[J]. J Virol, 2017, 91(18): e00478-17. DOI: 10.1128/JVI.00478-17.
    [38] ROEHLEN N, ROCA SUAREZ AA, EL SAGHIRE H, et al. Tight junction proteins and the biology of hepatobiliary disease[J]. Int J Mol Sci, 2020, 21(3): 825. DOI: 10.3390/ijms21030825.
    [39] BAKTASH Y, MADHAV A, COLLER KE, et al. Single particle imaging of polarized hepatoma organoids upon hepatitis C virus infection reveals an ordered and sequential entry process[J]. Cell Host Microbe, 2018, 23(3): 382-394. e5. DOI: 10.1016/j.chom.2018.02.005.
    [40] ELLENBROEK SI, IDEN S, COLLARD JG. Cell polarity proteins and cancer[J]. Semin Cancer Biol, 2012, 22(3): 208-215. DOI: 10.1016/j.semcancer.2012.02.012.
    [41] LU M, WU J, HAO ZW, et al. Basolateral CD147 induces hepatocyte polarity loss by E-cadherin ubiquitination and degradation in hepatocellular carcinoma progress[J]. Hepatology, 2018, 68(1): 317-332. DOI: 10.1002/hep.29798.
    [42] WANG C, CHENG Y, ZHANG X, et al. Vacuolar protein sorting 33B is a tumor suppressor in hepatocarcinogenesis[J]. Hepatology, 2018, 68(6): 2239-2253. DOI: 10.1002/hep.30077.
    [43] LIN H, HUANG H, YU Y, et al. Nerve growth factor regulates liver cancer cell polarity and motility[J]. Mol Med Rep, 2021, 23(4): 288. DOI: 10.3892/mmr.2021.11927.
    [44] HENKEL SA, SQUIRES JH, AYERS M, et al. Expanding etiology of progressive familial intrahepatic cholestasis[J]. World J Hepatol, 2019, 11(5): 450-463. DOI: 10.4254/wjh.v11.i5.450.
    [45] WEI CS, BECHER N, FRⅡS JB, et al. New tight junction protein 2 variant causing progressive familial intrahepatic cholestasis type 4 in adults: A case report[J]. World J Gastroenterol, 2020, 26(5): 550-561. DOI: 10.3748/wjg.v26.i5.550.
    [46] XU J, KAUSALYA PJ, van HUL N, et al. Protective functions of ZO-2/Tjp2 expressed in hepatocytes and cholangiocytes against liver injury and cholestasis[J]. Gastroenterology, 2021, 160(6): 2103-2118. DOI: 10.1053/j.gastro.2021.01.027.
    [47] STALKE A, SGODDA M, CANTZ T, et al. KIF12 Variants and disturbed hepatocyte polarity in children with a phenotypic spectrum of cholestatic liver disease[J]. J Pediatr, 2022, 240: 284-291. e9. DOI: 10.1016/j.jpeds.2021.09.019.
  • 加载中
表(1)
计量
  • 文章访问数:  82
  • HTML全文浏览量:  41
  • PDF下载量:  30
  • 被引次数: 0
出版历程
  • 收稿日期:  2022-03-15
  • 录用日期:  2022-04-25
  • 出版日期:  2022-11-20
  • 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