肝胆汁酸摄取转运蛋白和HBV进入受体NTCP的分子调控

StephenW

Molecular regulation of the hepatic bile acid uptake transporter and HBV entry receptor NTCP
Monique D Appelman  1 , Jochen M Wettengel  2 , Ulrike Protzer  3 , Ronald P J Oude Elferink  4 , Stan F J van de Graaf  5
Affiliations
Affiliations

    1
    Tytgat Institute for Liver and Intestinal Research, Amsterdam University Medical Centers Amsterdam, the Netherlands; Amsterdam Gastroenterology, Endocrinology, Metabolism (AGEM), Amsterdam, the Netherlands.
    2
    Institute of Virology, Technische Universität München/Helmholtz Zentrum München, Munich, Germany.
    3
    Institute of Virology, Technische Universität München/Helmholtz Zentrum München, Munich, Germany; German Center for Infection Research (DZIF), Munich partner site, Munich, Germany.
    4
    Tytgat Institute for Liver and Intestinal Research, Amsterdam University Medical Centers Amsterdam, the Netherlands; Amsterdam Gastroenterology, Endocrinology, Metabolism (AGEM), Amsterdam, the Netherlands; Department of Gastroenterology and Hepatology, Amsterdam University Medical Centers, University of Amsterdam, Amsterdam, the Netherlands.
    5
    Tytgat Institute for Liver and Intestinal Research, Amsterdam University Medical Centers Amsterdam, the Netherlands; Amsterdam Gastroenterology, Endocrinology, Metabolism (AGEM), Amsterdam, the Netherlands; Department of Gastroenterology and Hepatology, Amsterdam University Medical Centers, University of Amsterdam, Amsterdam, the Netherlands. Electronic address: [email protected].

    PMID: 33932583 DOI: 10.1016/j.bbalip.2021.158960

Abstract

Transporters expressed by hepatocytes and enterocytes play a critical role in maintaining the enterohepatic circulation of bile acids. The sodium taurocholate cotransporting polypeptide (NTCP), exclusively expressed at the basolateral side of hepatocytes, mediates the uptake of conjugated bile acids. In conditions where bile flow is impaired (cholestasis), pharmacological inhibition of NTCP-mediated bile acid influx is suggested to reduce hepatocellular damage due to bile acid overload. Furthermore, NTCP has been shown to play an important role in hepatitis B virus (HBV) and hepatitis Delta virus (HDV) infection by functioning as receptor for viral entry into hepatocytes. This review provides a summary of current molecular insight into the regulation of NTCP expression at the plasma membrane, hepatic bile acid transport, and NTCP-mediated viral infection.

Keywords: ASBT; BSEP; Cholestasis; HBV; HDV.

Copyright © 2021. Published by Elsevier B.V.

StephenW

肝胆汁酸摄取转运蛋白和HBV进入受体NTCP的分子调控
Monique D Appelman 1，Jochen M Wettengel 2，Ulrike Protzer 3，Ronald P J Oude Elferink 4，Stan F J van de Graaf 5
隶属关系
隶属关系

    1个
    阿姆斯特丹大学医学中心，Tytgat肝脏和肠道研究所，荷兰阿姆斯特丹；阿姆斯特丹胃肠病学，内分泌代谢学（AGEM），阿姆斯特丹，荷兰。
    2个
    慕尼黑工业大学/ Helmholtz Zentrum慕尼黑病毒研究所，德国慕尼黑。
    3
    慕尼黑工业大学病毒研究所，德国慕尼黑德国感染研究中心（DZIF），慕尼黑合作伙伴地点，德国慕尼黑。
    4
    阿姆斯特丹大学医学中心，Tytgat肝脏和肠道研究所，荷兰阿姆斯特丹；阿姆斯特丹胃肠病学，内分泌代谢学（AGEM），荷兰阿姆斯特丹；荷兰阿姆斯特丹大学阿姆斯特丹大学医学中心胃肠病学和肝病学系。
    5
    阿姆斯特丹大学医学中心，Tytgat肝脏和肠道研究所，荷兰阿姆斯特丹；阿姆斯特丹胃肠病学，内分泌代谢学（AGEM），荷兰阿姆斯特丹；荷兰阿姆斯特丹大学阿姆斯特丹大学医学中心胃肠病学和肝病学系。电子地址：[email protected]。

    PMID：33932583 DOI：10.1016 / j.bbalip.2021.158960

抽象的

肝细胞和肠上皮细胞表达的转运蛋白在维持胆汁酸的肠肝循环中起着至关重要的作用。牛磺胆酸钠共转运多肽（NTCP）仅在肝细胞的基底外侧表达，介导了结合胆汁酸的摄取。在胆汁流量受损（胆汁淤积）的情况下，建议对NTCP介导的胆汁酸涌入进行药理抑制，以减少由于胆汁酸超负荷引起的肝细胞损害。此外，已显示NTCP通过充当病毒进入肝细胞的受体，在乙型肝炎病毒（HBV）和丙型肝炎三角洲病毒（HDV）感染中起重要作用。这篇综述提供了对分子质膜上NTCP表达的调节，肝胆汁酸转运和NTCP介导的病毒感染的当前分子认识的总结。

关键字：ASBT； BSEP；胆汁淤积;乙肝病毒; HDV。

版权所有©2021. Elsevier B.V.发布

StephenW

https://www.sciencedirect.com/sc ... 21000883?via%3Dihub