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

顶端钠依赖性胆汁酸转运蛋白(ASBT)在肝胆疾病中的作用

谢晓暄 杜丽娜 郭紫云 杨燕

引用本文:
Citation:

顶端钠依赖性胆汁酸转运蛋白(ASBT)在肝胆疾病中的作用

DOI: 10.12449/JCH240133
基金项目: 

国家自然科学基金 (82205184)

北京市属医院科研培育计划 (PZ2022027)

利益冲突声明:本文不存在任何利益冲突。
作者贡献声明:谢晓暄负责文献检索及文章撰写;杜丽娜负责文章修改;郭紫云负责文献检索;杨燕负责指导及校正。
详细信息
    通信作者:

    杨燕, yy2303@sina.com (ORCID: 0000-0003-1070-9614)

Role of apical sodium-dependent bile acid transporter in hepatobiliary diseases

Research funding: 

National Natural Science Foundation of China (82205184);

Bejing Municipal Administration of Hospital Incubating Program (PZ2022027)

More Information
    Corresponding author: YANG yan, yy2303@sina.com (ORCID: 0000-0003-1070-9614)
  • 摘要: 顶端钠依赖性胆汁酸转运蛋白(ASBT)是负责胆汁酸肠道重吸收的关键转运体,对维持胆汁酸和胆固醇稳态起重要作用,其表达受到转录因子、核受体和肠道微生物等多种因素的调控。ASBT的表达和功能异常会导致胆汁酸及胆固醇代谢紊乱,引起多种肝胆相关疾病。目前,ASBT作为一种治疗靶点已受到广泛关注。本文阐述了ASBT的生物学特征及表达调控机制,并对ASBT在肝胆疾病中的作用进行了综述,为相关疾病的治疗提供新方向。

     

  • [1] XIAO L, PAN GY. An important intestinal transporter that regulates the enterohepatic circulation of bile acids and cholesterol homeostasis: The apical sodium-dependent bile acid transporter(SLC10A2/ASBT)[J]. Clin Res Hepatol Gastroenterol, 2017, 41( 5): 509- 515. DOI: 10.1016/j.clinre.2017.02.001.
    [2] LUO ZL, CHENG L, WANG T, et al. Bile acid transporters are expressed and heterogeneously distributed in rat bile ducts[J]. Gut Liver, 2019, 13( 5): 569- 575. DOI: 10.5009/gnl18265.
    [3] LI M, WANG Q, LI Y, et al. Apical sodium-dependent bile acid transporter, drug target for bile acid related diseases and delivery target for prodrugs: Current and future challenges[J]. Pharmacol Ther, 2020, 212: 107539. DOI: 10.1016/j.pharmthera.2020.107539.
    [4] LI J, ZHENG KY, ZHANG BB. Mechanism of action of bile acid metabolism in regulating cholestatic liver disease and the research and development of drugs[J]. J Clin Hepatol, 2021, 37( 10): 2482- 2487. DOI: 10.3969/j.issn.1001-5256.2021.10.048.

    李静, 郑葵阳, 张蓓蓓. 胆汁酸代谢调节胆汁淤积性肝病的作用机制及药物研发[J]. 临床肝胆病杂志, 2021, 37( 10): 2482- 2487. DOI: 10.3969/j.issn.1001-5256.2021.10.048.
    [5] WANG XD, LYU Y, JI YJ, et al. An engineered disulfide bridge traps and validates an outward-facing conformation in a bile acid transporter[J]. Acta Crystallogr D Struct Biol, 2021, 77( Pt 1): 108- 116. DOI: 10.1107/S205979832001517X.
    [6] KAZGAN N, METUKURI MR, PURUSHOTHAM A, et al. Intestine-specific deletion of SIRT1 in mice impairs DCoH2-HNF-1α-FXR signaling and alters systemic bile acid homeostasis[J]. Gastroenterology, 2014, 146( 4): 1006- 1016. DOI: 10.1053/j.gastro.2013.12.029.
    [7] LIU S, LIU M, ZHANG ML, et al. Transcription factor Klf9 controls bile acid reabsorption and enterohepatic circulation in mice via promoting intestinal Asbt expression[J]. Acta Pharmacol Sin, 2022, 43( 9): 2362- 2372. DOI: 10.1038/s41401-021-00850-x.
    [8] MA L, JÜTTNER M, KULLAK-UBLICK GA, et al. Regulation of the gene encoding the intestinal bile acid transporter ASBT by the caudal-type homeobox proteins CDX1 and CDX2[J]. Am J Physiol Gastrointest Liver Physiol, 2012, 302( 1): G123- G133. DOI: 10.1152/ajpgi.00102.2011.
    [9] YANG N, DONG YQ, JIA GX, et al. ASBT(SLC10A2): A promising target for treatment of diseases and drug discovery[J]. Biomed Pharmacother, 2020, 132: 110835. DOI: 10.1016/j.biopha.2020.110835.
    [10] NGUYEN JT, RIESSEN R, ZHANG TY, et al. Deletion of intestinal SHP impairs short-term response to cholic acid challenge in male mice[J]. Endocrinology, 2021, 162( 8): bqab063. DOI: 10.1210/endocr/bqab063.
    [11] SONNE DP. Mechanisms in endocrinology: FXR signalling: A novel target in metabolic diseases[J]. Eur J Endocrinol, 2021, 184( 5): R193- R205. DOI: 10.1530/EJE-20-1410.
    [12] OUT C, PATANKAR JV, DOKTOROVA M, et al. Gut microbiota inhibit Asbt-dependent intestinal bile acid reabsorption via Gata4[J]. J Hepatol, 2015, 63( 3): 697- 704. DOI: 10.1016/j.jhep.2015.04.030.
    [13] CHAUDHARI SN, LUO JN, HARRIS DA, et al. A microbial metabolite remodels the gut-liver axis following bariatric surgery[J]. Cell Host Microbe, 2021, 29( 3): 408- 424. e 7. DOI: 10.1016/j.chom.2020.12.004.
    [14] HASSAN S, HERTEL P. Overview of progressive familial intrahepatic cholestasis[J]. Clin Liver Dis, 2022, 26( 3): 371- 390. DOI: 10.1016/j.cld.2022.03.003.
    [15] van der MARK VA, de WAART DR, HO-MOK KS, et al. The lipid flippase heterodimer ATP8B1-CDC50A is essential for surface expression of the apical sodium-dependent bile acid transporter(SLC10A2/ASBT) in intestinal Caco-2 cells[J]. Biochim Biophys Acta, 2014, 1842( 12 Pt A): 2378- 2386. DOI: 10.1016/j.bbadis.2014.09.003.
    [16] THOMPSON RJ, ARNELL H, ARTAN R, et al. Odevixibat treatment in progressive familial intrahepatic cholestasis: A randomised, placebo-controlled, phase 3 trial[J]. Lancet Gastroenterol Hepatol, 2022, 7( 9): 830- 842. DOI: 10.1016/S2468-1253(22)00093-0.
    [17] SHIRLEY M. Maralixibat: First approval[J]. Drugs, 2022, 82( 1): 71- 76. DOI: 10.1007/s40265-021-01649-0.
    [18] KAMATH BM, GOLDSTEIN A, HOWARD R, et al. Maralixibat treatment response in alagille syndrome is associated with improved health-related quality of life[J]. J Pediatr, 2023, 252: 68- 75.e5. DOI: 10.1016/j.jpeds.2022.09.001.
    [19] KUNST RF, de WAART DR, WOLTERS F, et al. Systemic ASBT inactivation protects against liver damage in obstructive cholestasis in mice[J]. JHEP Rep, 2022, 4( 11): 100573. DOI: 10.1016/j.jhepr.2022.100573.
    [20] CABALLERO-CAMINO FJ, RODRIGUES PM, WÅNGSELL F, et al. A3907, a systemic ASBT inhibitor, improves cholestasis in mice by multiorgan activity and shows translational relevance to humans[J]. Hepatology, 2023. DOI: 10.1097/HEP.0000000000000376.[ Online ahead of print]
    [21] ZHOU L, WANG XT, SONG FL, et al. Effect of Huayu Lidan decoction combined with a comprehensive intervention in the treatment of patients with intrahepatic cholestasis of pregnancy[J]. J Changchun Univ Chin Med, 2022, 38( 11): 1234- 1237. DOI: 10.13463/j.cnki.cczyy.2022.11.014.

    周璐, 王希涛, 宋风丽, 等. 化瘀利胆汤结合综合干预治疗妊娠期肝内胆汁淤积症[J]. 长春中医药大学学报, 2022, 38( 11): 1234- 1237. DOI: 10.13463/j.cnki.cczyy.2022.11.014.
    [22] WANG LR, LIU J. Role of miR-221/222 and its target genes in the pathogenesis of intrahepatic cholestasis of pregnancy[J]. J Chongqing Med Univ, 2019, 44( 5): 662- 667. DOI: 10.13406/j.cnki.cyxb.001937.

    王林若, 刘建. miR-221/222及其靶基因在妊娠期肝内胆汁淤积症发病机制中作用的研究[J]. 重庆医科大学学报, 2019, 44( 5): 662- 667. DOI: 10.13406/j.cnki.cyxb.001937.
    [23] ONTSOUKA E, EPSTEIN A, KALLOL S, et al. Placental expression of bile acid transporters in intrahepatic cholestasis of pregnancy[J]. Int J Mol Sci, 2021, 22( 19): 10434. DOI: 10.3390/ijms221910434.
    [24] OVADIA C, PERDONES-MONTERO A, SPAGOU K, et al. Enhanced microbial bile acid deconjugation and impaired ileal uptake in pregnancy repress intestinal regulation of bile acid synthesis[J]. Hepatology, 2019, 70( 1): 276- 293. DOI: 10.1002/hep.30661.
    [25] MEADOWS V, MARAKOVITS C, EKSER B, et al. Loss of apical sodium bile acid transporter alters bile acid circulation and reduces biliary damage in cholangitis[J]. Am J Physiol Gastrointest Liver Physiol, 2023, 324( 1): G60- G77. DOI: 10.1152/ajpgi.00112.2022.
    [26] MIETHKE AG, ZHANG WJ, SIMMONS J, et al. Pharmacological inhibition of apical sodium-dependent bile acid transporter changes bile composition and blocks progression of sclerosing cholangitis in multidrug resistance 2 knockout mice[J]. Hepatology, 2016, 63( 2): 512- 523. DOI: 10.1002/hep.27973.
    [27] GAO LX, WANG L, WOO E, et al. Clinical management of primary biliary cholangitis-strategies and evolving trends[J]. Clin Rev Allergy Immunol, 2020, 59( 2): 175- 194. DOI: 10.1007/s12016-019-08772-7.
    [28] AL-DURY S, WAHLSTRÖM A, WAHLIN S, et al. Pilot study with IBAT inhibitor A4250 for the treatment of cholestatic pruritus in primary biliary cholangitis[J]. Sci Rep, 2018, 8( 1): 6658. DOI: 10.1038/s41598-018-25214-0.
    [29] CHENG SH, ZOU M, LIU QH, et al. Activation of constitutive androstane receptor prevents cholesterol gallstone formation[J]. Am J Pathol, 2017, 187( 4): 808- 818. DOI: 10.1016/j.ajpath.2016.12.013.
    [30] FERKINGSTAD E, ODDSSON A, GRETARSDOTTIR S, et al. Genome-wide association meta-analysis yields 20 loci associated with gallstone disease[J]. Nat Commun, 2018, 9( 1): 5101. DOI: 10.1038/s41467-018-07460-y.
    [31] WANG CE, XU WT, GONG J, et al. Research progress in the treatment of nonalcoholic fatty liver disease[J]. Chin J Med Offic, 2022, 50( 9): 897- 899, 903. DOI: 10.16680/j.1671-3826.2022.09.06.

    王彩娥, 许文涛, 宫建, 等. 非酒精性脂肪性肝病治疗研究进展[J]. 临床军医杂志, 2022, 50( 9): 897- 899, 903. DOI: 10.16680/j.1671-3826.2022.09.06.
    [32] GILLARD J, CLERBAUX LA, NACHIT M, et al. Bile acids contribute to the development of non-alcoholic steatohepatitis in mice[J]. JHEP Rep, 2021, 4( 1): 100387. DOI: 10.1016/j.jhepr.2021.100387.
    [33] van de PEPPEL IP, BERTOLINI A, van DIJK TH, et al. Efficient reabsorption of transintestinally excreted cholesterol is a strong determinant for cholesterol disposal in mice[J]. J Lipid Res, 2019, 60( 9): 1562- 1572. DOI: 10.1194/jlr.M094607.
    [34] SALIC K, KLEEMANN R, WILKINS-PORT C, et al. Apical sodium-dependent bile acid transporter inhibition with volixibat improves metabolic aspects and components of non-alcoholic steatohepatitis in Ldlr-/-. Leiden mice[J]. PLoS One, 2019, 14( 6): e0218459. DOI: 10.1371/journal.pone.0218459.
    [35] van de PEPPEL IP, RAO A, DOMMERHOLT MB, et al. The beneficial effects of apical sodium-dependent bile acid transporter inactivation depend on dietary fat composition[J]. Mol Nutr Food Res, 2020, 64( 24): e2000750. DOI: 10.1002/mnfr.202000750.
    [36] RAO A, van de PEPPEL IP, GUMBER S, et al. Attenuation of the hepatoprotective effects of ileal apical sodium dependent bile acid transporter(ASBT) inhibition in choline-deficient L-amino acid-defined(CDAA) diet-fed mice[J]. Front Med, 2020, 7: 60. DOI: 10.3389/fmed.2020.00060.
    [37] MATYE DJ, WANG HW, LUO WY, et al. Combined ASBT inhibitor and FGF15 treatment improves therapeutic efficacy in experimental nonalcoholic steatohepatitis[J]. Cell Mol Gastroenterol Hepatol, 2021, 12( 3): 1001- 1019. DOI: 10.1016/j.jcmgh.2021.04.013.
    [38] LIU YL, LIU T, ZHAO X, et al. New insights into the bile acid-based regulatory mechanisms and therapeutic perspectives in alcohol-related liver disease[J]. Cell Mol Life Sci, 2022, 79( 9): 486. DOI: 10.1007/s00018-022-04509-6.
    [39] MATYE DJ, LI Y, CHEN C, et al. Gut-restricted apical sodium-dependent bile acid transporter inhibitor attenuates alcohol-induced liver steatosis and injury in mice[J]. Alcohol Clin Exp Res, 2021, 45( 6): 1188- 1199. DOI: 10.1111/acer.14619.
  • 加载中
计量
  • 文章访问数:  46
  • HTML全文浏览量:  16
  • PDF下载量:  11
  • 被引次数: 0
出版历程
  • 收稿日期:  2023-03-29
  • 录用日期:  2023-05-06
  • 出版日期:  2024-01-23
  • 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