Role of anion exchanger 2 in the pathogenesis of primary biliary cholangitis

Xi CHU; Lianjun XING

doi:10.3969/j.issn.1001-5256.2021.03.044

Volume 37 Issue 3

Mar. 2021

Turn off MathJax

Article Contents

Article Navigation > Journal of Clinical Hepatology > 2021 > 37(3): 718-720

PDF( 1952 KB)

Role of anion exchanger 2 in the pathogenesis of primary biliary cholangitis

DOI: 10.3969/j.issn.1001-5256.2021.03.044

Xi CHU,
Lianjun XING^,

Second Department of Spleen and Stomach, Longhua Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai 200000, China

Received Date: 2020-09-13
Accepted Date: 2020-11-16
Published Date: 2021-03-20

Abstract

Abstract

The etiology and pathogenesis of primary biliary cholangitis (PBC) remain unclear at present, and it is believed that the change in bile duct microenvironment and autoimmune response are the main factors for the onset of this disease. Anion exchanger 2 (AE2) is an HCO₃^-/Cl^- exchange protein located on the membrane of epithelial cells and has been taken seriously by scholars since studies have shown that it can induce and aggravate PBC. This article summarizes the role of AE2 in bile duct microenvironment and autoimmune response from the aspects of AE2 and related regulatory mechanisms and further analyzes the pathogenesis of PBC, so as to find new therapies and diagnostic and prognostic indicators for PBC by exploring the regulatory mechanism of AE2 in PBC.
- Primary Biliary Cholangitis,
- Antiporters,
- Pathologic Processes

FullText(HTML)

References(32)

References

[1]	CHEN CW, CHENG J, DOU XG, et al. Consensus on the diagnosis and management of primary biliary cirrhosis(cholangitis)(2015)[J]. J Clin Hepatol, 2015, 31(12): 1980-1988. DOI: 10.3969/j.issn.1001-5256.2015.12.004 陈成伟, 成军, 窦晓光, 等. 原发性胆汁性肝硬化(又名原发性胆汁性胆管炎)诊断和治疗共识(2015)[J]. 临床肝胆病杂志, 2015, 31(12): 1980-1988. DOI: 10.3969/j.issn.1001-5256.2015.12.004
[2]	ZENG N, DUAN W, CHEN S, et al. Epidemiology and clinical course of primary biliary cholangitis in the Asia-Pacific region: A systematic review and meta-analysis[J]. Hepatol Int, 2019, 13(6): 788-99. DOI: 10.1007/s12072-019-09984-x
[3]	LINDOR KD, BOWLUS CL, BOYER J, et al. Primary biliary cholangitis: 2018 practice guidance from the American Association for the Study of Liver Diseases[J]. Hepatology, 2019, 69(1): 394-419.
[4]	RODRIGUES PM, PERUGORRIA MJ, SANTOS-LASO A, et al. Primary biliary cholangitis: A tale of epigenetically-induced secretory failure?[J]. J Hepatol, 2018, 69(6): 1371-1383. DOI: 10.1016/j.jhep.2018.08.020
[5]	TERZIROLI BERETTA-PICCOLI B, MIELI-VERGANI G, VERGANI D, et al. The challenges of primary biliary cholangitis: What is new and what needs to be done[J]. J Autoimmun, 2019, 105: 102328. DOI: 10.1016/j.jaut.2019.102328
[6]	ROMERO MF, CHEN AP, PARKER MD, et al. The SLC4 family of bicarbonate (HCO₃) transporters[J]. Mol Aspects Med, 2013, 34(2-3): 159-182. DOI: 10.1016/j.mam.2012.10.008
[7]	MEDINA JF. Role of the anion exchanger 2 in the pathogenesis and treatment of primary biliary cirrhosis[J]. Dig Dis, 2011, 29(1): 103-112. DOI: 10.1159/000324144
[8]	ARENAS F, HERVIAS I, URIZ M, et al. Combination of ursodeoxycholic acid and glucocorticoids upregulates the AE2 alternate promoter in human liver cells[J]. J Clin Invest, 2008, 118(2): 695-709.
[9]	CORPECHOT C, CARRAT F, BAHR A, et al. The effect of ursodeoxycholic acid therapy on the natural course of primary biliary cirrhosis[J]. Gastroenterology, 2005, 128(2): 297-303. DOI: 10.1053/j.gastro.2004.11.009
[10]	KIM S, HAN SY, YU KS, et al. Impaired autophagy promotes bile acid-induced hepatic injury and accumulation of ubiquitinated proteins[J]. Biochem Biophys Res Commun, 2018, 495(1): 1541-1547. DOI: 10.1016/j.bbrc.2017.11.202
[11]	MARIN JJ, MACIAS RI, BRIZ O, et al. Bile acids in physiology, pathology and pharmacology[J]. Curr Drug Metab, 2015, 17(1): 4-29. DOI: 10.2174/1389200216666151103115454
[12]	BEUERS U, HOHENESTER S, DE BUY WENNIGER LJ, et al. The biliary HCO(3)(-) umbrella: A unifying hypothesis on pathogenetic and therapeutic aspects of fibrosing cholangiopathies[J]. Hepatology, 2010, 52(4): 1489-1496. DOI: 10.1002/hep.23810
[13]	MISZCZUK GS, BANALES JM, ZUCCHETTI AE, et al. Adaptive downregulation of Cl^-/HCO₃^- exchange activity in rat hepatocytes under experimental obstructive cholestasis[J]. PLoS One, 2019, 14(2): e0212215. DOI: 10.1371/journal.pone.0212215
[14]	HISAMOTO S, SHIMODA S, HARADA K, et al. Hydrophobic bile acids suppress expression of AE2 in biliary epithelial cells and induce bile duct inflammation in primary biliary cholangitis[J]. J Autoimmun, 2016, 75: 150-160. DOI: 10.1016/j.jaut.2016.08.006
[15]	HOHENESTER S, WENNIGER LM, PAULUSMA CC, et al. A biliary HCO₃^- umbrella constitutes a protective mechanism against bile acid-induced injury in human cholangiocytes[J]. Hepatology, 2012, 55(1): 173-183. DOI: 10.1002/hep.24691
[16]	CHANG JC, GO S, DE WAART DR, et al. Soluble adenylyl cyclase regulates bile salt-induced apoptosis in human cholangiocytes[J]. Hepatology, 2016, 64(2): 522-534. DOI: 10.1002/hep.28550
[17]	SALAS JT, BANALES JM, SARVIDE S, et al. Ae2a, b-deficient mice develop antimitochondrial antibodies and other features resembling primary biliary cirrhosis[J]. Gastroenterology, 2008, 134(5): 1482-1493. DOI: 10.1053/j.gastro.2008.02.020
[18]	TRAUNER M, FICKERT P, BAGHDASARYAN A, et al. New insights into autoimmune cholangitis through animal models[J]. Dig Dis, 2010, 28(1): 99-104. DOI: 10.1159/000282072
[19]	CONCEPCION AR, SALAS JT, SÁEZ E, et al. CD8⁺T cells undergo activation and programmed death-1 repression in the liver of aged Ae2a, b-/- mice favoring autoimmune cholangitis[J]. Oncotarget, 2015, 6(30): 28588-28606. DOI: 10.18632/oncotarget.5665
[20]	CELAY J, LOZANO T, CONCEPCION AR, et al. Targeting the anion exchanger 2 with specific peptides as a new therapeutic approach in B lymphoid neoplasms[J]. Haematologica, 2018, 103(6): 1065-1072. DOI: 10.3324/haematol.2017.175687
[21]	MA WT, CHEN DK. Immunological abnormalities in patients with primary biliary cholangitis[J]. Clin Sci (Lond), 2019, 133(6): 741-760. DOI: 10.1042/CS20181123
[22]	CONCEPCION AR, SALAS JT, SARVIDE S, et al. Anion exchanger 2 is critical for CD8(+) T cells to maintain pHi homeostasis and modulate immune responses[J]. Eur J Immunol, 2014, 44(5): 1341-1351. DOI: 10.1002/eji.201344218
[23]	ARENAS F, HERVÍAS I, SÁEZ E, et al. Promoter hypermethylation of the AE2/SLC4A2 gene in PBC[J]. JHEP Rep, 2019, 1(3): 145-153. DOI: 10.1016/j.jhepr.2019.05.006
[24]	XU LN, LI Y, PENG JY. microRNA and drug-induced liver injury[J]. Chin J Clin Pharmacol Ther, 2020, 25(7): 803-809. https://www.cnki.com.cn/Article/CJFDTOTAL-YLZL202007015.htm 许丽娜, 李月, 彭金咏. microRNA与药物性肝损伤[J]. 中国临床药理学与治疗学, 2020, 25(7): 803-809. https://www.cnki.com.cn/Article/CJFDTOTAL-YLZL202007015.htm
[25]	MO H, XU M. Research progress of microRNA-1290 in digestive system tumors[J]. China Med Herald, 2020, 17(29): 48-51. https://www.cnki.com.cn/Article/CJFDTOTAL-YYCY202029014.htm 莫辉, 徐岷. microRNA-1290在消化系统肿瘤中的研究进展[J]. 中国医药导报, 2020, 17(29): 48-51. https://www.cnki.com.cn/Article/CJFDTOTAL-YYCY202029014.htm
[26]	PADGETT KA, LAN RY, LEUNG PC, et al. Primary biliary cirrhosis is associated with altered hepatic microRNA expression[J]. J Autoimmun, 2009, 32(3-4): 246-253. DOI: 10.1016/j.jaut.2009.02.022
[27]	SZABO G, BALA S. MicroRNAs in liver disease[J]. Nat Rev Gastroenterol Hepatol, 2013, 10(9): 542-552. DOI: 10.1038/nrgastro.2013.87
[28]	ERICE O, MUNOZ-GARRIDO P, VAQUERO J, et al. MicroRNA-506 promotes primary biliary cholangitis-like features in cholangiocytes and immune activation[J]. Hepatology, 2018, 67(4): 1420-1440. DOI: 10.1002/hep.29533
[29]	BANALES JM, SÁEZ E, URIZ M, et al. Up-regulation of microRNA 506 leads to decreased Cl^-/HCO₃^- anion exchanger 2 expression in biliary epithelium of patients with primary biliary cirrhosis[J]. Hepatology, 2012, 56(2): 687-697. DOI: 10.1002/hep.25691
[30]	HONG JH, MUHAMMAD E, ZHENG C, et al. Essential role of carbonic anhydrase XⅡ in secretory gland fluid and HCO₃(-) secretion revealed by disease causing human mutation[J]. J Physiol, 2015, 593(24): 5299-5312. DOI: 10.1113/JP271378
[31]	HWANG S, SHIN DM, HONG JH. Drug repurposing as an antitumor agent: Disulfiram-mediated carbonic anhydrase 12 and anion exchanger 2 modulation to inhibit cancer cell migration[J]. Molecules, 2019, 24(18): 3409. DOI: 10.3390/molecules24183409
[32]	WANG W, REN X, CAI Y, et al. Rifampicin induces bicarbonate-rich choleresis in rats: Involvement of anion exchanger 2[J]. Dig Dis Sci, 2016, 61(1): 126-136. DOI: 10.1007/s10620-015-3850-2

Relative Articles

Supplements(0)

Cited By

Proportional views

Proportional views

通讯作者: 陈斌, bchen63@163.com

1.
沈阳化工大学材料科学与工程学院沈阳 110142

Get Citation

PDF

XML

Article Metrics

Article views (502) PDF downloads(32)

Role of anion exchanger 2 in the pathogenesis of primary biliary cholangitis

DOI: 10.3969/j.issn.1001-5256.2021.03.044

Abstract

References

Proportional views

Catalog

通讯作者: 陈斌, bchen63@163.com

Article Metrics

Proportional views

Related

Role of anion exchanger 2 in the pathogenesis of primary biliary cholangitis

DOI: 10.3969/j.issn.1001-5256.2021.03.044

Abstract

References

Proportional views

Catalog

通讯作者: 陈斌, bchen63@163.com

Article Metrics

Proportional views

Related

About Journal

Submission Guideline

Journal Online

Hepatobiliary College

Guidelines

Export File

Citation

Format

Content