肝X受体——肝纤维化治疗新的分子靶点-CSCIED科技核心评价数据库-手机版

肝X受体——肝纤维化治疗新的分子靶点

Liver X receptor——a new molecular target for the treatment of liver fibrosis

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DOI
刊名	生命的化学
年，卷(期)	2019, 39(03)
作者	杨兰馨1肖元芬1杨玉容1张素君2涂剑1,
作者单位	1.南华大学药物药理研究所2.南华大学医学研究中心
摘要	肝X受体(liver X receptor, LXR)具有典型的核受体结构,包含LXRα(NR1H3)和LXRβ(NR1H2)两种同源亚型。作为一种多功能的转录因子,LXRα可诱导参与胆固醇逆转运、肝糖原代谢以及脂肪酸合成的基因表达,且能抑制一系列炎症反应。LXR特别是LXRα不仅在肝纤维化进程中异常低表达,而且在病毒性肝炎、酒精性和非酒精性脂肪肝等形成的肝纤维化疾病中均发挥了一定的作用,提示LXRα与肝纤维化有密切关系。因此,本文就LXR在肝纤维化中发挥的调节作用展开综述。
Abstract	Liver X receptor(LXR) includes two homologous subtypes, LXRα(NR1H3) and LXRβ(NR1H2),which has a typical structure belonging to nuclear receptors. As a multifunctional transcription factor, LXRαcan not only induce gene expression involved in reverse cholesterol transport, hepatic glycogen metabolism,and fatty acid synthesis, but also inhibit a range of inflammatory responses. In recent years, LXR, especially LXRα, can be found expressed lower during liver fibrosis. Furthermore, it is important for LXRα to attend in liver fibrosis originating from viral hepatitis, alcoholic and nonalcoholic fatty liver, and so on. All above suggest that there are close relationship between LXRα and liver fibrosis. Therefore, this work will briefly introduce about the regulatory role of LXR in liver fibrosis.
关键词	肝X受体;肝纤维化;新靶点;
KeyWord	liver X receptor;liver fibrosis;new target
基金项目
页码	458-463

参考文献
相关文献

[1] Pradat P, Virlogeux V, Trepo E. Epidemiology and elimination of HCV- related liver disease. Viruses, 2018, 10(10): 1- 18

[2] Affo S, Yu LX, Schwabe RF. The role of cancer- associated fibroblasts and fibrosis in liver cancer. Annu Rev Pathol, 2017, 12: 153- 186

[3] Ingiliz P, Valantin MA, Preziosi P, et al. Influence of interferon- based therapy on liver fibrosis progression in HIV/HCV coinfected patients: a retrospective repeated liver biopsy analysis. J Hepatol, 2012, 56(1): 49- 54

[4] 陈应康, 余福强, 刘大腾, 等. 水飞蓟宾葡甲胺盐对肝纤维化大鼠的疗效和可能机制. 中国免疫学杂志, 2017, 33(3): 360- 364

[5] Hamilton JP, Koganti L, Muchenditsi A, et al. Activation of liver X receptor/retinoid X receptor pathway ameliorates liver disease in Atp7B- - /- (Wilson disease) mice. Hepatology, 2016, 63(6): 1828- 1841

[6] Griffett K, Burris TP. Promiscuous activity of the LXR antagonist GSK2033 in a mouse model of fatty liver disease. Biochem Biophys Res Commun, 2016, 479(3): 424- 428

[7] Willy PJ, Umesono K, Ong ES, et al. LXR: a nuclear receptor that defines a distinct retinoid response pathway. Genes Dev, 1995, 9(9): 1033- 1045

[8] Kelly DP. Introduction to the nuclear receptor review series. Circ Res, 2010, 106(10): 1557- 1558

[9] Zhang Y, Breevoort SR, Angdisen J, et al. Liver LXRa expression is crucial for whole body cholesterol homeostasis and reverse cholesterol transport in mice. J Clin Invest, 2012, 122(5): 1688- 1699

[10] Zhang L, Reue K, Fong LG, et al. Feedback regulation of cholesterol uptake by the LXR- IDOL- LDLR axis. Arterioscler Thromb Vasc Biol, 2012, 32(11): 2541- 2546

[11] Zhao XY, Xiong X, Liu T, et al. Long noncoding RNA licensing of obesity- linked hepatic lipogenesis and NAFLD pathogenesis. Nat Commun, 2018, 9(1): 2986

[12] Beyer C, Huang J, Beer J, et al. Activation of liver X receptors inhibits experimental fibrosis by interfering with interleukin- 6 release from macrophages. Ann Rheum Dis, 2015, 74(6): 1317- 1324

[13] Bai T, Yao YL, Jin XJ, et al. Acanthoic acid, a diterpene in Acanthopanax koreanum, ameliorates the development of liver fibrosis via LXRs signals. Chem Biol Interact, 2014, 218: 63- 70

[14] 林元灿, 骆海莺. 垂盆草总黄酮对实验性肝纤维化干预作用的研究. 中华中医药学刊, 2015, 33(8): 1962-1964

[15] Li X, Wang Z, Klaunig JE. Modulation of xenobiotic nuclear receptors in high- fat diet induced non- alcoholic fatty liver disease. Toxicology, 2018, 410: 199- 213

[16] Huang P, Kaluba B, Jiang XL, et al. Liver X Receptor Inverse Agonist SR9243 Suppresses Nonalcoholic Steatohepatitis Intrahepatic Inflammation and Fibrosis. Biomed Res Int, 2018, 2018: 8071093

[17] Marroni CA, Fleck AM, Fernandes SA, et al. Liver transplantation and alcoholic liver disease: History, controversies, and considerations. World J Gastroenterol, 2018, 24(26): 2785- 2805

[18] Ren JJ, Huang TJ, Zhang QQ, et al. Insulin- like growth factor binding protein related protein 1 knockdown attenuates hepatic fibrosis via the regulation of MMPs/TIMPs in mice. Hepatobiliary Pancreat Dis Int, 2019, 18(1): 38- 47

[19] Jamhiri I, Shahin K, Khodabandeh Z, et al. Recombinant NS3 protein induced expression of immune modulatory elements in hepatic stellate cells during its fibrotic activity. Viral Immunol, 2018, 31(8): 575- 582

[20] Ilan Y, Shailubhai K, Sanyal A. Immunotherapy with oral administration of humanized anti- CD3 monoclonal antibody: A novel gut- immune system- based therapy for metaflammation and NASH. Clin Exp Immunol, 2018, 193(3): 275- 283

[21] Miotto N, Mendes LC, Zanaga LP, et al. Predictors of early discontinuation of interferon- free direct antiviral agents in patients with hepatitis C virus and advanced liver fibrosis: results of a real- life cohort. Eur J Gastroenterol Hepatol, 2017, 29(10): 1149- 1154

[22] Di FM, Moulin P, Roy P, et al. Homozygous MTTP and APOB mutations may lead to hepatic steatosis and fibrosis despite metabolic differences in congenital hypocholesterolemia. J Hepatol, 2014, 61(4): 891- 902

[23] Aguayo- Orozco A, Bois FY, Brunak S, et al. Analysis of time- series gene expression data to explore mechanisms of chemical- induced hepatic steatosis toxicity. Front Genet, 2018, 9: 396

[24] Schmeltzer PA, Russo MW. Clinical narrative: autoimmune hepatitis. Am J Gastroenterol, 2018, 113(7): 951- 958

[25] Wu J, Wu Q, Wu M et al. Serum cystatin C predicts mortality in HBV- related decompensated cirrhosis. Biomed Res Int, 2019, doi: 10.1155/2019/7272045

[26] Jin L, Chen N, Liu JF, et al. Anti- fibrotic effect of oxymatrine in the assisted treatment of HCV- induced cirrhosis. Zhonghua Gan Zang Bing Za Zhi, 2018, 26(6): 460- 462

[27] Al- Qahtani AA, Al- Anazi MR, Nazir N, et al. Hepatitis B virus (HBV) X gene mutations and their association with liver disease progression in HBV- infected patients. Oncotarget, 2017, 8(62): 105115- 105125

[28] Luo N, Cai Y, Zhang J, et al. The C- terminal region of the hepatitis B virus X protein is required for its stimulation of HBV replication in primary mouse hepatocytes. Virus Res, 2012, 165(2): 170- 178

[29] Li C, Lin C, Cong X, et al. PDK1- WNK1 signaling is affected by HBx and involved in the viability and metastasis of hepatic cells. Oncol Lett, 2018, 15(4): 5940- 5946

[30] Lin HJ, Ku KL, Lin IH, et al. Naringenin attenuates hepatitis B virus X protein- induced hepatic steatosis. BMC Complement Altern Med, 2017, 17(1): 505

[31] Kim HY, Cho HK, Kim HH, et al. Oxygenated derivatives of cholesterol promote hepatitis B virus gene expression through nuclear receptor LXRα activation. Virus Res, 2011, 158(1- 2): 55- 61

[32] 郑燕珊, 倪仰鹏, 陈理明, 等. 核受体LXRα在HBV阳性肝硬化及原发性肝癌组织中的表达及意义. 海南医学, 2014, 25(15): 2185- 2188

[33] 王晶晶, 刘顺爱, 张锦前, 等. HCV核心蛋白通过LXRα核受体介导HepG2细胞甘油三酯合成增加. 中华实验和临床感染病杂志, 2014, 8(1): 6- 9

[34] Pisonero- Vaquero S, Garcia- Mediavilla MV, Jorquera F, et al. Modulation of PI3K- LXRα- dependent lipogenesis mediated by oxidative/nitrosative stress contributes to inhibition of HCV replication by quercetin. Lab Invest, 2014, 94(3): 262- 274

[35] 陈军, 邱泽文, 高文婷, 等. LXR- alpha/SREBP- 1c通路参与HCV NS5A诱导的肝细胞脂质代谢紊乱. 中国生物化学与分子生物学报, 2014, 30(12): 1231- 1235

[36] Wang M, Sun S, Wu T, et al. Inhibition of LXRα/SREBP- 1c- Mediated Hepatic Steatosis By Jiang- Zhigranule. Evid Based Complement Alternat Med, 2013, 2013: 584634

[37] Ducheix S, Montagner A, Polizzi A, et al. Essential fatty acids deficiency promotes lipogenic gene expression and hepatic steatosis through the liver X receptor. J Hepatol, 2013, 58(5): 984- 992

[38] Zhang YH, Ma Q, Ding P, et al. S100A4 gene is crucial for methionine- choline- deficient diet- induced non- alcoholic fatty liver disease in mice. Yonsei Med J, 2018, 59(9): 1064- 1071

[39] Jiang W, Huang S, Teng H, et al. Diagnostic accuracy of point shear wave elastography and transient elastography for staging hepatic fibrosis in patients with non- alcoholic fatty liver disease: a meta- analysis. BMJ Open, 2018, 8(8): e021787

[40] Kim JA, Song SB, Yang SY, et al. Components from the steamed leaves of Acanthopanax koreanum and their effects on PPAR activity in HepG2 cells. Nat Prod Commun, 2011, 6(9): 1233- 1236

[41] Lu ZY, Shao Z, Li YL, et al. Prevalence of and risk factors for non- alcoholic fatty liver disease in a Chinese population: An 8- year follow- up study. World J Gastroenterol, 2016, 22(13): 3663- 3669

[42] Younossi ZM, Koenig AB, Abdelatif D, et al. Global epidemiology of nonalcoholic fatty liver disease- Meta- analytic assessment of prevalence, incidence, and outcomes. Hepatology, 2016, 64(1): 73- 84

[43] 龚享文, 杨钦河, 闫海震, 等. 疏肝健脾方药对LXRα/FAS信号通路介导非酒精性脂肪性肝病大鼠肝细胞脂肪沉积的影响. 中国中西医结合杂志, 2014, 34(12): 1481- 1486

[44] Ahn SB, Jang K, Jun DW, et al. Expression of liver X receptor correlates with intrahepatic inflammation and fibrosis in patients with nonalcoholic fatty liver disease. Dig Dis Sci, 2014, 59(12): 2975- 2982

[45] Sim WC, Park S, Lee KY, et al. LXR- α antagonist meso- dihydroguaiaretic acid attenuates high- fat diet- induced nonalcoholic fatty liver. Biochem Pharmacol, 2014, 90(4): 414- 424

[46] 黄妙珍, 傅珍春, 谢军军, 等. 血府逐瘀汤对非酒精性脂肪性肝病大鼠肝脏LXR- α表达的影响. 上海中医药杂志, 2012, 46(12): 70- 72

[47] Tanaka N, Aoyama T, Kimura S, et al. Targeting nuclear receptors for the treatment of fatty liver disease. Pharmacol Ther, 2017, 179: 142- 157

[48] O'Mahony F, Wroblewski K, O'Byrne SM, et al. Liver X receptors balance lipid stores in hepatic stellate cells through Rab18, a retinoid responsive lipid droplet protein. Hepatology, 2015, 62(2): 615- 626

[49] Han YP. Matrix metalloproteinases, the pros and cons, in liver fibrosis. J Gastroenterol Hepatol, 2006, 21(s3): S88- S91

[50] Xing Y, Zhao T, Gao X, et al. Liver X receptor α is essential for the capillarization of liver sinusoidal endothelial cells in liver injury. Sci Rep, 2016, 6: 21309

[51] Xie G, Choi SS, Syn WK, et al. Hedgehog signalling regulates liver sinusoidal endothelial cell capillarisation. Gut, 2013, 62(2): 299- 309

[52] Xie G, Wang X, Wang L, et al. Role of differentiation of liver sinusoidal endothelial cells in progression and regression of hepatic fibrosis in rats. Gastroenterology, 2012, 142(4): 918- 927

[53] Wu Y, Liu X, Zhou Q, et al. Silent information regulator 1 (SIRT1) ameliorates liver fibrosis via promoting activated stellate cell apoptosis and reversion. Toxicol Appl Pharmacol, 2015, 289(2): 163- 176

[54] Liu L, Liu C, Zhang Q, et al. SIRT1- mediated transcriptional regulation of SOX2 is important for self- renewal of liver cancer stem cells. Hepatology, 2016, 64(3): 814- 827

[55] Lin XL, Liu MH, Hu HJ, et al. Curcumin enhanced cholesterol efflux by upregulating ABCA1 expression through AMPK- SIRT1- LXRα signaling in THP- 1 macrophage- derived foam cells. DNA Cell Biol, 2015, 34(9): 561- 572

[56] Beaven SW, Wroblewski K, Wang J, et al. Liver X receptor signaling is a determinant of stellate cell activation and susceptibility to fibrotic liver disease. Gastroenterology, 2011, 140(3): 1052- 1062

引用本文

杨兰馨肖元芬杨玉容张素君涂剑. 肝X受体——肝纤维化治疗新的分子靶点 [J]. 生命的化学. 2019; 39; (03). 458 - 463.

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