内科理论与实践 ›› 2022, Vol. 17 ›› Issue (01): 4-10.doi: 10.16138/j.1673-6087.2022.01.002
潘琼, 李明巧, 谭雅, 余思睿, 柴进(
)
收稿日期:2021-11-24
出版日期:2022-02-28
发布日期:2022-07-25
通讯作者:
柴进
E-mail:jin.chai@cldcsw.org
基金资助:
Received:2021-11-24
Online:2022-02-28
Published:2022-07-25
中图分类号:
潘琼, 李明巧, 谭雅, 余思睿, 柴进. 胆酸转运蛋白调控胆汁酸代谢的分子机制[J]. 内科理论与实践, 2022, 17(01): 4-10.
图1
胆汁酸的肝肠循环及代谢调控 RXR：维A酸X受体（retinoid X receptor）;SHP：小异二聚体伴侣（small heterodimer partner）;FGF：成纤维细胞生长因子19（fibroblast growth factor 19）。
| [1] |
Chawla A, Saez E, Evans RM. “Don’t know much bile-ology”[J]. Cell, 2000, 103(1): 1-4.
pmid: 11051540 |
| [2] |
Russell DW. The enzymes, regulation, and genetics of bile acid synthesis[J]. Annu Rev Biochem, 2003, 72: 137-174.
pmid: 12543708 |
| [3] |
Trauner M, Meier PJ, Boyer JL. Molecular pathogenesis of cholestasis[J]. N Engl J Med, 1998, 339(17): 1217-1227.
doi: 10.1056/NEJM199810223391707 URL |
| [4] |
Ghonem NS, Assis DN, Boyer JL. Fibrates and cholestasis[J]. Hepatology, 2015, 62(2): 635-643.
doi: 10.1002/hep.27744 URL |
| [5] |
Cai SY, Boyer JL. Bile infarcts: new insights into the pathogenesis of obstructive cholestasis[J]. Hepatology, 2019, 69(2): 473-475.
doi: 10.1002/hep.30291 URL |
| [6] |
Chai J, He Y, Cai SY, et al. Elevated hepatic multidrug resistance-associated protein 3/ATP-binding cassette subfamily C 3 expression in human obstructive cholestasis is mediated through tumor necrosis factor alpha and c-Jun NH2-terminal kinase/stress-activated protein kinase-signaling pathway[J]. Hepatology, 2012, 55(5): 1485-1494.
doi: 10.1002/hep.24801 pmid: 22105759 |
| [7] |
Chai J, Cai SY, Liu X, et al. Canalicular membrane MRP2/ABCC2 internalization is determined by Ezrin Thr567 phosphorylation in human obstructive cholestasis[J]. J Hepatol, 2015, 63(6): 1440-1448.
doi: 10.1016/j.jhep.2015.07.016 pmid: 26212029 |
| [8] | Chai J, Luo D, Wu X, et al. Changes of organic anion transporter MRP4 and related nuclear receptors in human obstructive cholestasis[J]. J Gastrointest Sur, 2011, 15(6): 996-1004. |
| [9] |
Pan Q, Zhang X, Zhang L, et al. Solute carrier organic anion transporter family member 3A1 is a bile acid efflux transporter in cholestasis[J]. Gastroenterology, 2018, 155(5): 1578-1592.
doi: 10.1053/j.gastro.2018.07.031 URL |
| [10] |
Corpechot C, Chazouillères O, Rousseau A, et al. A placebo-controlled trial of bezafibrate in primary biliary cholangitis[J]. N Engl J Med, 2018, 378(23): 2171-2181.
doi: 10.1056/NEJMoa1714519 URL |
| [11] |
Schwarz M, Russell DW, Dietschy JM, et al. Alternate pathways of bile acid synthesis in the cholesterol 7α-hydroxylase knockout mouse are not upregulated by either cholesterol or cholestyramine feeding[J]. J Lipid Res, 2001, 42(10): 1594-1603.
pmid: 11590215 |
| [12] |
Kullak-Ublick GA, Stieger B, Meier PJ. Enterohepatic bile salt transporters in normal physiology and liver disease[J]. Gastroenterology, 2004, 126(1): 322-342.
doi: 10.1053/j.gastro.2003.06.005 pmid: 14699511 |
| [13] |
Trauner M, Boyer JL. Bile salt transporters: molecular characterization, function, and regulation[J]. Physiol Rev, 2003, 83(2): 633-671.
doi: 10.1152/physrev.00027.2002 URL |
| [14] |
Lefebvre P, Cariou B, Lien F, et al. Role of bile acids and bile acid receptors in metabolic regulation[J]. Physiol Rev, 2009, 89(1): 147-191.
doi: 10.1152/physrev.00010.2008 URL |
| [15] |
Slijepcevic D, Kaufman C, Wichers CG, et al. Impaired uptake of conjugated bile acids and hepatitis B virus pres1-binding in Na+-taurocholate cotransporting polypeptide knockout mice[J]. Hepatology, 2015, 62(1): 207-219.
doi: 10.1002/hep.27694 pmid: 25641256 |
| [16] |
Halilbasic E, Claudel T, Trauner M. Bile acid transporters and regulatory nuclear receptors in the liver and beyond[J]. J Hepatol, 2013, 58(1): 155-168.
doi: 10.1016/j.jhep.2012.08.002 pmid: 22885388 |
| [17] |
Dawson PA, Lan T, Rao A. Bile acid transporters[J]. J Lipid Res, 2009, 50(12): 2340-2357.
doi: 10.1194/jlr.R900012-JLR200 pmid: 19498215 |
| [18] |
Slijepcevic D, Roscam Abbing RLP, Fuchs CD, et al. Na+-taurocholate cotransporting polypeptide inhibition has hepatoprotective effects in cholestasis in mice[J]. Hepatology, 2018, 68(3): 1057-1069.
doi: 10.1002/hep.29888 pmid: 29572910 |
| [19] |
Vaz FM, Paulusma CC, Huidekoper H, et al. Sodium taurocholate cotransporting polypeptide (SLC10A1) deficiency: conjugated hypercholanemia without a clear clinical phenotype[J]. Hepatology, 2015, 61(1): 260-267.
doi: 10.1002/hep.27240 URL |
| [20] |
Liu R, Chen C, Xia X, et al. Homozygous p.Ser267Phe in SLC10A1 is associated with a new type of hypercholanemia and implications for personalized medicine[J]. Sci Rep, 2017, 7(1): 9214.
doi: 10.1038/s41598-017-07012-2 URL |
| [21] | Pan Q, Luo G, Qu J, et al. A homozygous R148W mutation in semaphorin 7A causes progressive familial intrahepatic cholestasis[J]. EMBO Mol Med, 2021, 13(11): e14563. |
| [22] | Donkers JM, Kooijman S, Slijepcevic D, et al. NTCP deficiency in mice protects against obesity and hepatosteatosis[J]. JCI Insight, 2019, 5(14): e127197. |
| [23] |
Nigam SK, Bush KT, Martovetsky G, et al. The organic anion transporter (OAT) family: a systems biology perspective[J]. Physiol Rev, 2015, 95(1): 83-123.
doi: 10.1152/physrev.00025.2013 URL |
| [21] |
Halilbasic E, Claudel T, Trauner M. Bile acid transporters and regulatory nuclear receptors in the liver and beyond[J]. J Hepatol, 2013, 58(1): 155-168.
doi: 10.1016/j.jhep.2012.08.002 pmid: 22885388 |
| [24] |
Csanaky IL, Lu H, Zhang Y, et al. Organic anion-transporting polypeptide 1b2 (Oatp1b2) is important for the hepatic uptake of unconjugated bile acids: studies in Oatp1b2-null mice[J]. Hepatology, 2011, 53(1): 272-281.
doi: 10.1002/hep.23984 pmid: 20949553 |
| [25] |
van de Steeg E, Stránecky V, Hartmannová H, et al. Complete OATP1B1 and OATP1B3 deficiency causes human Rotor syndrome by interrupting conjugated bilirubin reuptake into the liver[J]. J Clin Invest, 2012, 122(2): 519-528.
doi: 10.1172/JCI59526 URL |
| [26] |
Ballatori N, Christian WV, Lee JY, et al. OSTα-OSTβ: a major basolateral bile acid and steroid transporter in human intestinal, renal, and biliary epithelia[J]. Hepatology, 2005, 42(6): 1270-1279.
doi: 10.1002/hep.20961 URL |
| [27] |
Soroka CJ, Mennone A, Hagey LR, et al. Mouse organic solute transporter alpha deficiency enhances renal excretion of bile acids and attenuates cholestasis[J]. Hepatology, 2010, 51(1): 181-190.
doi: 10.1002/hep.23265 pmid: 19902485 |
| [28] |
Sultan M, Rao A, Elpeleg O, et al. Organic solute transporter-β (SLC51B) deficiency in two brothers with congenital diarrhea and features of cholestasis[J]. Hepatology, 2018, 68(2): 590-598.
doi: 10.1002/hep.29516 pmid: 28898457 |
| [29] |
Gao E, Cheema H, Waheed N, et al. Organic solute transporter alpha deficiency: a disorder with cholestasis, liver fibrosis, and congenital diarrhea[J]. Hepatology, 2020, 71(5): 1879-1882.
doi: 10.1002/hep.31087 URL |
| [30] |
Boyer JL, Soroka CJ. Bile formation and secretion: an update[J]. J Hepatol, 2021, 75(1): 190-201.
doi: 10.1016/j.jhep.2021.02.011 URL |
| [31] |
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 URL |
| [32] |
Kubitz R, Dröge C, Kluge S, et al. Autoimmune BSEP disease: disease recurrence after liver transplantation for progressive familial intrahepatic cholestasis[J]. Clin Rev Allergy Immunol, 2015, 48(2-3): 273-284.
doi: 10.1007/s12016-014-8457-4 URL |
| [33] |
Cao W, Kayama H, Chen ML, et al. The xenobiotic transporter Mdr1 enforces T cell homeostasis in the presence of intestinal bile acids[J]. Immunity, 2017, 47(6): 1182-1196.
doi: 10.1016/j.immuni.2017.11.012 URL |
| [34] |
Kipp H, Arias IM. Trafficking of canalicular ABC transporters in hepatocytes[J]. Annu Rev Physiol, 2002, 64: 595-608.
doi: 10.1146/annurev.physiol.64.081501.155793 URL |
| [35] |
Lang C, Meier Y, Stieger B, et al. Mutations and polymorphisms in the bile salt export pump and the multidrug resistance protein 3 associated with drug-induced liver injury[J]. Pharmacogenet Genomics, 2007, 17(1): 47-60.
doi: 10.1097/01.fpc.0000230418.28091.76 URL |
| [36] |
Gautherot J, Delautier D, Maubert MA, et al. Phosphorylation of ABCB4 impacts its function: insights from disease-causing mutations[J]. Hepatology, 2014, 60(2): 610-621.
doi: 10.1002/hep.27170 pmid: 24723470 |
| [37] |
Stieger B. Role of the bile salt export pump, BSEP, in acquired forms of cholestasis[J]. Drug Metab Rev, 2010, 42(3): 437-445.
doi: 10.3109/03602530903492004 pmid: 20028269 |
| [38] |
Nies AT, Keppler D. The apical conjugate efflux pump ABCC2 (MRP2)[J]. Pflugers Arch, 2007, 453(5): 643-659.
doi: 10.1007/s00424-006-0109-y URL |
| [39] |
Beer AJ, Hertz D, Seemann E, et al. Reduced Mrp2 surface availability as PI3Kγ-mediated hepatocytic dysfunction reflecting a hallmark of cholestasis in sepsis[J]. Sci Rep, 2020, 10(1): 13110.
doi: 10.1038/s41598-020-69901-3 URL |
| [40] |
Bohan A, Chen WS, Denson LA, et al. Tumor necrosis factor alpha-dependent up-regulation of LRH-1 and MRP3(ABCC3) reduces liver injury in obstructive cholestasis[J]. J Biol Chem, 2003, 278(38): 36688-36698.
doi: 10.1074/jbc.M304011200 pmid: 12837754 |
| [41] | Chen W, Cai SY, Xu S, et al. Nuclear receptors RXRα: RARα are repressors for human MRP3 expression[J]. Am J Physiol Gastrointest Liver Physiol, 2007, 292(5): G1221-G1227. |
| [42] |
Zhang X, Wang T, Yang Y, et al. Tanshinone ⅡA attenuates acetaminophen-induced hepatotoxicity through HOTAIR-Nrf2-MRP2/4 signaling pathway[J]. Biomed Pharmacother, 2020, 130: 110547.
doi: 10.1016/j.biopha.2020.110547 URL |
| [43] |
Vollrath V, Wielandt AM, Iruretagoyena M, et al. Role of Nrf2 in the regulation of the Mrp2(ABCC2) gene[J]. Biochem J, 2006, 395(3): 599-609.
doi: 10.1042/BJ20051518 pmid: 16426233 |
| [44] |
Schuetz EG, Strom S, Yasuda K, et al. Disrupted bile acid homeostasis reveals an unexpected interaction among nuclear hormone receptors, transporters, and cytochrome P450[J]. J Biol Chem, 2001, 276(42): 39411-39418.
doi: 10.1074/jbc.M106340200 pmid: 11509573 |
| [45] |
Mennone A, Soroka CJ, Cai SY, et al. MRP4-/- mice have an impaired cytoprotective response in obstructive cholestasis[J]. Hepatology, 2006, 43(5): 1013-1021.
pmid: 16628672 |
| [46] |
Keppler D. The roles of MRP2, MRP3, OATP1B1, and OATP1B3 in conjugated hyperbilirubinemia[J]. Drug Metab Dispos, 2014, 42(4): 561-565.
doi: 10.1124/dmd.113.055772 URL |
| [47] |
Fang C, Filipp FV, Smith JW. Unusual binding of ursodeoxycholic acid to ileal bile acid binding protein: role in activation of FXRα[J]. J Lipid Res, 2012, 53(4): 664-673.
doi: 10.1194/jlr.M021733 URL |
| [48] |
Harris MJ, Kagawa T, Dawson PA, et al. Taurocholate transport by hepatic and intestinal bile acid transporters is independent of FIC1 overexpression in Madin-Darby canine kidney cells[J]. J Gastroenterol Hepatol, 2004, 19(7): 819-825.
doi: 10.1111/j.1440-1746.2004.03347.x URL |
| [49] |
Richter D, Harsch S, Strohmeyer A, et al. MALDI-TOF mass spectrometry screening of cholelithiasis risk markers in the gene of HNF1α[J]. J Proteomics, 2012, 75(12): 3386-3399.
doi: 10.1016/j.jprot.2012.04.036 URL |
| [50] |
Chen F, Ma L, Sartor RB, et al. Inflammatory-mediated repression of the rat ileal sodium-dependent bile acid transporter by c-fos nuclear translocation[J]. Gastroenterology, 2002, 123(6): 2005-2016.
doi: 10.1053/gast.2002.37055 URL |
| [51] |
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 pmid: 33035828 |
| [52] |
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 URL |
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