Mechanism of taurocholic acid in promoting the progression of liver cirrhosis

Yingbiao YUE; Kunhua WANG; Lei ZOU

doi:10.3969/j.issn.1001-5256.2021.11.037

Volume 37 Issue 11

Nov. 2021

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Article Navigation > Journal of Clinical Hepatology > 2021 > 37(11): 2658-2662

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Mechanism of taurocholic acid in promoting the progression of liver cirrhosis

DOI: 10.3969/j.issn.1001-5256.2021.11.037

1.
NHC Key Laboratory of Drug Addiction Medicine, Department of Gastrointestinal and Hernia Surgery, The First Affiliated Hospital of Kunming Medical University, Scientific Research Laboratory Center, The First Affiliated Hospital of Kunming Medical University, Kunming Medical University, Kunming 650032, China
2.
NHC Key Laboratory of Drug Addiction Medicine, Department of Hepatobiliary Surgery, The First Affiliated Hospital of Kunming Medical University, Kunming 650032, China

Research funding:

The National Natural Science Foundation of China (81870458);

Yunnan Engineering Technology Center of Digestive Disease (2018DH006);

Yunnan Engineering Technology Center of Digestive Disease (ZX2019-03-03);

Yunling Scholar (YLXL20170002)

Received Date: 2021-04-06
Accepted Date: 2021-05-08
Published Date: 2021-11-20

Abstract

Abstract

Bile acid is the main component of bile, and the external secretion of bile acid into the intestine can help with the absorption of lipids and fat-soluble vitamins; in addition, bile acid acts as a signal molecule to regulate bile acid metabolism and help maintain intestinal homeostasis. The process of liver cirrhosis is accompanied by varying degrees of cholestasis, causing bile duct injury, and exposure of liver cells to a high concentration of bile acid will accelerate the progression of liver cirrhosis and form a vicious circle. Among these abnormally elevated bile acids, taurocholic acid (TCA) shows the greatest increase, suggesting that TCA may play an important role in the process of liver cirrhosis. At present, there are relatively few studies on the mechanism of TCA in liver cirrhosis, and current studies in China and globally have shown that TCA at a high concentration (≥50 μmol/L) can promote the progression of liver cirrhosis by acting on liver cells (hepatic stellate cells, hepatocytes, hepatic progenitor cells, and bile duct epithelial cells). This article discusses the detailed mechanism of TCA in promoting liver cirrhosis and points out that TCA has the clinical potential as a biomarker and therapeutic target for liver cirrhosis.
- Taurocholic Acid,
- Liver Cirrhosis,
- Cholestasis

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References(41)

References

[1]	BARNETT R. Liver cirrhosis[J]. Lancet, 2018, 392(10144): 275. DOI: 10.1016/S0140-6736(18)31659-3.
[2]	PAROLA M, PINZANI M. Liver fibrosis: Pathophysiology, pathogenetic targets and clinical issues[J]. Mol Aspects Med, 2019, 65: 37-55. DOI: 10.1016/j.mam.2018.09.002.
[3]	TROTTIER J, BIAŁEK A, CARON P, et al. Profiling circulating and urinary bile acids in patients with biliary obstruction before and after biliary stenting[J]. PLoS One, 2011, 6(7): e22094. DOI: 10.1371/journal.pone.0022094.
[4]	JIA W, WEI M, RAJANI C, et al. Targeting the alternative bile acid synthetic pathway for metabolic diseases[J]. Protein Cell, 2021, 12(5): 411-425. DOI: 10.1007/s13238-020-00804-9.
[5]	KIRIYAMA Y, NOCHI H. The biosynthesis, signaling, and neurological functions of bile acids[J]. Biomolecules, 2019, 9(6): 232. DOI: 10.3390/biom9060232.
[6]	TICHO AL, MALHOTRA P, DUDEJA PK, et al. Intestinal absorption of bile acids in health and disease[J]. Compr Physiol, 2019, 10(1): 21-56. DOI: 10.1002/cphy.c190007.
[7]	KOK B, ABRALDES JG. Child-Pugh classification: Time to abandon?[J]. Semin Liver Dis, 2019, 39(1): 96-103. DOI: 10.1055/s-0038-1676805.
[8]	RIMINI M, ROVESTI G, CASADEI-GARDINI A. Child Pugh and ALBI grade: Past, present or future?[J]. Ann Transl Med, 2020, 8(17): 1044. DOI: 10.21037/atm-20-3709.
[9]	WANG X, XIE G, ZHAO A, et al. Serum bile acids are associated with pathological progression of hepatitis B-induced cirrhosis[J]. J Proteome Res, 2016, 15(4): 1126-1134. DOI: 10.1021/acs.jproteome.5b00217.
[10]	LIU Z, ZHANG Z, HUANG M, et al. Taurocholic acid is an active promoting factor, not just a biomarker of progression of liver cirrhosis: Evidence from a human metabolomic study and in vitro experiments[J]. BMC Gastroenterol, 2018, 18(1): 112. DOI: 10.1186/s12876-018-0842-7.
[11]	HORVATITS T, DROLZ A, ROEDL K, et al. Serum bile acids as marker for acute decompensation and acute-on-chronic liver failure in patients with non-cholestatic cirrhosis[J]. Liver Int, 2017, 37(2): 224-231. DOI: 10.1111/liv.13201.
[12]	KHOMICH O, IVANOV AV, BARTOSCH B. Metabolic hallmarks of hepatic stellate cells in liver fibrosis[J]. Cells, 2019, 9(1): 24. DOI: 10.3390/cells9010024.
[13]	MU M, ZUO S, WU RM, et al. Ferulic acid attenuates liver fibrosis and hepatic stellate cell activation via inhibition of TGF-β/Smad signaling pathway[J]. Drug Des Devel Ther, 2018, 12: 4107-4115. DOI: 10.2147/DDDT.S186726.
[14]	FAN Y, LI Y, CHU Y, et al. Toll-like receptors recognize intestinal microbes in liver cirrhosis[J]. Front Immunol, 2021, 12: 608498. DOI: 10.3389/fimmu.2021.608498.
[15]	SEKI E, de MINICIS S, OSTERREICHER CH, et al. TLR4 enhances TGF-beta signaling and hepatic fibrosis[J]. Nat Med, 2007, 13(11): 1324-1332. DOI: 10.1038/nm1663.
[16]	FABREGAT I, CABALLERO-DíAZ D. Transforming growth factor-β-induced cell plasticity in liver fibrosis and hepatocarcinogenesis[J]. Front Oncol, 2018, 8: 357.
[17]	CAJA L, DITURI F, MANCARELLA S, et al. TGF-β and the tissue microenvironment: Relevance in fibrosis and cancer[J]. Int J Mol Sci, 2018, 19(5): 1294. DOI: 10.3390/ijms19051294.
[18]	GHAFOORY S, VARSHNEY R, ROBISON T, et al. Platelet TGF-β1 deficiency decreases liver fibrosis in a mouse model of liver injury[J]. Blood Adv, 2018, 2(5): 470-480. DOI: 10.1182/bloodadvances.2017010868.
[19]	PAIK YH, SCHWABE RF, BATALLER R, et al. Toll-like receptor 4 mediates inflammatory signaling by bacterial lipopolysaccharide in human hepatic stellate cells[J]. Hepatology, 2003, 37(5): 1043-1055. DOI: 10.1053/jhep.2003.50182.
[20]	WEI S, MA X, ZHAO Y. Mechanism of hydrophobic bile acid-induced hepatocyte injury and drug discovery[J]. Front Pharmacol, 2020, 11: 1084. DOI: 10.3389/fphar.2020.01084.
[21]	ALLEN K, JAESCHKE H, COPPLE BL. Bile acids induce inflammatory genes in hepatocytes: A novel mechanism of inflammation during obstructive cholestasis[J]. Am J Pathol, 2011, 178(1): 175-186. DOI: 10.1016/j.ajpath.2010.11.026.
[22]	ALLEN K, KIM ND, MOON JO, et al. Upregulation of early growth response factor-1 by bile acids requires mitogen-activated protein kinase signaling[J]. Toxicol Appl Pharmacol, 2010, 243(1): 63-67. DOI: 10.1016/j.taap.2009.11.013.
[23]	GUJRAL JS, LIU J, FARHOOD A, et al. Functional importance of ICAM-1 in the mechanism of neutrophil-induced liver injury in bile duct-ligated mice[J]. Am J Physiol Gastrointest Liver Physiol, 2004, 286(3): G499-507. DOI: 10.1152/ajpgi.00318.2003.
[24]	CAI X, LI Z, ZHANG Q, et al. CXCL6-EGFR-induced Kupffer cells secrete TGF-β1 promoting hepatic stellate cell activation via the SMAD2/BRD4/C-MYC/EZH2 pathway in liver fibrosis[J]. J Cell Mol Med, 2018, 22(10): 5050-5061. DOI: 10.1111/jcmm.13787.
[25]	KIM ND, MOON JO, SLITT AL, et al. Early growth response factor-1 is critical for cholestatic liver injury[J]. Toxicol Sci, 2006, 90(2): 586-595. DOI: 10.1093/toxsci/kfj111.
[26]	MARRA F, ROMANELLI RG, GIANNINI C, et al. Monocyte chemotactic protein-1 as a chemoattractant for human hepatic stellate cells[J]. Hepatology, 1999, 29(1): 140-148. DOI: 10.1002/hep.510290107.
[27]	QUECK A, BODE H, USCHNER FE, et al. Systemic MCP-1 levels derive mainly from injured liver and are associated with complications in cirrhosis[J]. Front Immunol, 2020, 11: 354. DOI: 10.3389/fimmu.2020.00354.
[28]	RAMM GA, SHEPHERD RW, HOSKINS AC, et al. Fibrogenesis in pediatric cholestatic liver disease: Role of taurocholate and hepatocyte-derived monocyte chemotaxis protein-1 in hepatic stellate cell recruitment[J]. Hepatology, 2009, 49(2): 533-544. DOI: 10.1002/hep.22637.
[29]	LI L, WEI W, LI Z, et al. The spleen promotes the secretion of CCL2 and supports an M1 dominant phenotype in hepatic macrophages during liver fibrosis[J]. Cell Physiol Biochem, 2018, 51(2): 557-574. DOI: 10.1159/000495276.
[30]	SUN T, ANNUNZIATO S, TCHORZ JS. Hepatic ductular reaction: A double-edged sword[J]. Aging (Albany NY), 2019, 11(21): 9223-9224. DOI: 10.18632/aging.102386.
[31]	SATO K, MARZIONI M, MENG F, et al. Ductular reaction in liver diseases: pathological mechanisms and translational significances[J]. Hepatology, 2019, 69(1): 420-430. DOI: 10.1002/hep.30150.
[32]	POZNIAK KN, PEAREN MA, PEREIRA TN, et al. Taurocholate induces biliary differentiation of liver progenitor cells causing hepatic stellate cell chemotaxis in the ductular reaction: Role in pediatric cystic fibrosis liver disease[J]. Am J Pathol, 2017, 187(12): 2744-2757. DOI: 10.1016/j.ajpath.2017.08.024.
[33]	RUDDELL RG, KNIGHT B, TIRNITZ-PARKER JE, et al. Lymphotoxin-beta receptor signaling regulates hepatic stellate cell function and wound healing in a murine model of chronic liver injury[J]. Hepatology, 2009, 49(1): 227-239. DOI: 10.1002/hep.22597.
[34]	TIRNITZ-PARKER JE, OLYNYK JK, RAMM GA. Role of TWEAK in coregulating liver progenitor cell and fibrogenic responses[J]. Hepatology, 2014, 59(3): 1198-1201. DOI: 10.1002/hep.26701.
[35]	LAMIREAU T, ZOLTOWSKA M, LEVY E, et al. Effects of bile acids on biliary epithelial cells: Proliferation, cytotoxicity, and cytokine secretion[J]. Life Sci, 2003, 72(12): 1401-1411. DOI: 10.1016/s0024-3205(02)02408-6.
[36]	XIANG DM, SUN W, NING BF, et al. The HLF/IL-6/STAT3 feedforward circuit drives hepatic stellate cell activation to promote liver fibrosis[J]. Gut, 2018, 67(9): 1704-1715. DOI: 10.1136/gutjnl-2016-313392.
[37]	REMMLER J, SCHNEIDER C, TREUNER-KAUEROFF T, et al. Increased level of interleukin 6 associates with increased 90-day and 1-year mortality in patients with end-stage liver disease[J]. Clin Gastroenterol Hepatol, 2018, 16(5): 730-737. DOI: 10.1016/j.cgh.2017.09.017.
[38]	LABENZ C, TOENGES G, HUBER Y, et al. Raised serum Interleukin-6 identifies patients with liver cirrhosis at high risk for overt hepatic encephalopathy[J]. Aliment Pharmacol Ther, 2019, 50(10): 1112-1119. DOI: 10.1111/apt.15515.
[39]	DU PLESSIS J, VANHEEL H, JANSSEN CE, et al. Activated intestinal macrophages in patients with cirrhosis release NO and IL-6 that may disrupt intestinal barrier function[J]. J Hepatol, 2013, 58(6): 1125-1132. DOI: 10.1016/j.jhep.2013.01.038.
[40]	MANCINELLI R, ONORI P, GAUDIO E, et al. Taurocholate feeding to bile duct ligated rats prevents caffeic acid-induced bile duct damage by changes in cholangiocyte VEGF expression[J]. Exp Biol Med (Maywood), 2009, 234(4): 462-474. DOI: 10.3181/0808-RM-255.
[41]	GAUDIO E, BARBARO B, ALVARO D, et al. Vascular endothelial growth factor stimulates rat cholangiocyte proliferation via an autocrine mechanism[J]. Gastroenterology, 2006, 130(4): 1270-1282. DOI: 10.1053/j.gastro.2005.12.034.

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Mechanism of taurocholic acid in promoting the progression of liver cirrhosis

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Mechanism of taurocholic acid in promoting the progression of liver cirrhosis

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