前列腺素合酶在肝脏疾病中的作用

蔡杰; 卢佶翃; 高航; 万志康; 孙莹

doi:10.3969/j.issn.1001-5256.2020.09.052

前列腺素合酶在肝脏疾病中的作用

DOI: 10.3969/j.issn.1001-5256.2020.09.052

1. 徐州医科大学药学院
2. 江苏省新药研究和临床药学重点实验室

基金项目:

国家自然科学基金(81603179)；

详细信息

中图分类号: R575
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出版历程
- 出版日期: 2020-09-20

Role of prostaglandin E synthases in liver diseases

Department of Pharmacy, Xuzhou Medical University

Research funding:

摘要

摘要:
前列腺素E2(PGE2)是花生四烯酸产生的具有生物活性的多不饱和脂肪酸,其主要代谢器官是肝脏并对多种肝脏疾病具有重要的调控作用。前列腺素合酶(PGES)是PGE2合成途径中重要的末端限速酶,参与调控肝脏疾病的发生发展。主要总结了已有研究中各种PGES在肝损伤、肝炎和肝癌方面的作用,希望可以为进一步深入研究PGES在肝脏疾病中的作用提供参考依据。
- 肝疾病 /
- 前列腺素E类 /
- 基因表达调控
Abstract:
Prostaglandin E2( PGE2) is a bioactive polyunsaturated fatty acid produced by arachidonic acid,and it is mainly metabolized in the liver and has an important regulatory effect on various liver diseases. Prostaglandin E synthases( PGESs) are important terminal rate-limiting enzymes in the PGE2 synthesis pathway and are involved in the development and progression of liver disease. This article mainly summarizes the role of PGESs in liver injury,hepatitis,and liver cancer in existing studies,hoping to provide a reference for further research on the role of PGESs in liver diseases.
- liver diseases /
- prostaglandins E /
- gene expression regulation

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参考文献(40)

[1] D'SOUZA AA,DEVARAJAN PV. Asialoglycoprotein receptor mediated hepatocyte targeting-strategies and applications[J]. J Control Release,2015,203:126-139.

[2] HUBER M,KEPPLER D. Eicosanoids and the liver[J]. Prog Liver Dis,1990,9:117-141.

[3] ABECASSIS M,FALK JA,MAKOWKA L,et al. 16,16 Dimethyl prostaglandin E2 prevents the development of fulminant hepatitis and blocks the induction of monocyte/macrophage procoagulant activity after murine hepatitis virus strain 3 infection[J]. J Clin Invest,1987,80(3):881-889.

[4] MOHAMED YS,ABDELSALAM RM,ATTIA AS,et al. Regulation of liver regeneration by prostaglandin E2 and thromboxane A2 following partial hepatectomy in rats[J]. Naunyn Schmiedebergs Arch Pharmacol,2020,393(8):1437-1446.

[5] SHIMADA H,HASHIMOTO R,AOKI A,et al. The regulatory mechanism involved in the prostaglandin E2 disposition in carbon tetrachloride-induced liver injury[J]. Prostaglandins Leukot Essent Fatty Acids,2020,155:102081.

[6] NAKANISHI M,ROSENBERG DW. Multifaceted roles of PGE2in inflammation and cancer[J]. Semin Immunopathol,2013,35(2):123-137.

[7] RICCIOTTI E,FITZGERALD GA. Prostaglandins and inflammation[J]. Arterioscler Thromb Vasc Biol,2011,31(5):986-1000.

[8] CAO Y,NISHIHARA R,WU K,et al. Population-wide impact of long-term use of aspirin and the risk for cancer[J]. JAMA Oncol,2016,2(6):762-769.

[9] ZHAO X,XU Z,LI H. NSAIDs use and reduced metastasis in cancer patients:Results from a meta-analysis[J]. Sci Rep,2017,7(1):1875.

[10] Coxib and traditional NSAID Trialists'(CNT)Col aboration,BHALA N,EMBERSON J,et al. Vascular and upper gastrointestinal effects of non-steroidal anti-inflammatory drugs:Meta-analyses of individual participant data from randomised trials[J]. Lancet,2013,382(9894):769-779.

[11] PARK JY,PILLINGER MH,ABRAMSON SB. Prostaglandin E2synthesis and secretion:The role of PGE2 synthases[J]. Clin Immunol,2006,119(3):229-240.

[12] MURAKAMI M,KUDO I. Recent advances in molecular biology and physiology of the prostaglandin E2-biosynthetic pathway[J]. Prog Lipid Res,2004,43(1):3-35.

[13] HARA S,KAMEI D,SASAKI Y,et al. Prostaglandin E synthases:Understanding their pathophysiological roles through mouse genetic models[J]. Biochimie,2010,92(6):651-659.

[14] SELZNER N,RUDIGER H,GRAF R,et al. Protective strategies against ischemic injury of the liver[J]. Gastroenterology,2003,125(3):917-936.

[15] HUCKLE WR,HEPLER JR,RHEE SG,et al. Protein kinase C inhibits epidermal growth factor-dependent tyrosine phosphorylation of phospholipase C gamma and activation of phosphoinositide hydrolysis[J]. Endocrinology,1990,127(4):1697-1705.

[16] YAMADA T,TAKUSAGAWA F. PGH2 degradation pathway catalyzed by GSH-heme complex bound microsomal prostaglandin E2 synthase type 2:The first example of a dual-function enzyme[J]. Biochemistry,2007,46(28):8414-8424.

[17] NAKATANI Y,HOKONOHARA Y,TAJIMA Y,et al. Involvement of the constitutive prostaglandin E synthase cPGES/p23in expression of an initial prostaglandin E2 inactivating enzyme,15-PGDH[J]. Prostaglandins Other Lipid Mediat,2011,94(3-4):112-117.

[18] NISHIZAWA N,ITO Y,ESHIMA K,et al. Inhibition of microsomal prostaglandin E synthase-1 facilitates liver repair after hepatic injury in mice[J]. J Hepatol,2018,69(1):110-120.

[19] YAO L,CHEN W,HAN C,et al. Microsomal prostaglandin E synthase-1 protects against Fas-induced liver injury[J].Am J Physiol Gastrointest Liver Physiol,2016,310(11):G1071-1080.

[20] PIANKO S,PATELLA S,OSTAPOWICZ G,et al. Fas-mediated hepatocyte apoptosis is increased by hepatitis C virus infection and alcohol consumption,and may be associated with hepatic fibrosis:Mechanisms of liver cell injury in chronic hepatitis C virus infection[J]. J Viral Hepat,2001,8(6):406-413.

[21] SHARMA AD,NARAIN N,HNDEL EM,et al. MicroRNA-221 regulates FAS-induced fulminant liver failure[J]. Hepatology,2011,53(5):1651-1661.

[22] IBRAHIM SH,HIRSOVA P,GORES GJ. Non-alcoholic steatohepatitis pathogenesis:Sublethal hepatocyte injury as a driver of liver inflammation[J]. Gut,2018,67(5):963-972.

[23] SAYINER M,KOENIG A,HENRY L,et al. Epidemiology of nonalcoholic fatty liver disease and nonalcoholic steatohepatitis in the united states and the rest of the world[J]. Clin Liver Dis,2016,20(2):205-214.

[24] HENKEL J,FREDE K,SCHANZE N,et al. Stimulation of fat accumulation in hepatocytes by PGE-dependent repression of hepatic lipolysis，β-oxidation and VLDL-synthesis[J].Lab Invest,2012,92(11):1597-1606.

[25] TIAN Z,CHEN Y,GAO B. Natural killer cells in liver disease[J]. Hepatology,2013,57(4):1654-1662.

[26] HENKEL J,COLEMAN CD,SCHRAPLAU A,et al. Augmented liver inflammation in a microsomal prostaglandin E synthase 1(m PGES-1)-deficient diet-induced mouse NASH model[J]. Sci Rep,2018,8(1):16127.

[27] BRAY F,FERLAY J,SOERJOMATARAM I,et al. Global cancer statistics 2018:GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries[J]. CA Cancer J Clin,2018,68(6):394-424.

[28] LU D,HAN C,WU T. Microsomal prostaglandin E synthase-1 promotes hepatocarcinogenesis through activation of a novel EGR1/β-catenin signaling axis[J]. Oncogene,2012,31(7):842-857.

[29] BLBL B,KKGZEL I·．Microsomal prostaglandin E2synthase-1 as a new macromolecular drug target in the prevention of inflammation and cancer[J]. Anticancer Agents Med Chem,2019,19(10):1205-1222.

[30] LIU C,CHEN S,WANG X,et al. 15d-PGJ2decreases PGE2synthesis in HBx-positive liver cells by interfering EGR1 binding to m PGES-1 promoter[J]. Biochem Pharmacol,2014,91(3):337-347.

[31] RUAN D,SO SP. Prostaglandin E2 produced by inducible COX-2 and m PGES-1 promoting cancer cell proliferation in vitro and in vivo[J]. Life Sci,2014,116(1):43-50.

[32] MA Y,WANG X,TANG N. Downregulation of m PGES-1 expression via EGR1 plays an important role in inhibition of caffeine on PGE2 synthesis of HBx(+)hepatocytes[J]. Mediators Inflamm,2015,2015:372750.

[33] CHALASANI NP,HAYASHI PH,BONKOVSKY HL,et al. ACG Clinical Guideline:The diagnosis and management of idiosyncratic drug-induced liver injury[J]. Am J Gastroenterol,2014,109(7):950-966; quiz 967.

[34] REUBEN A,KOCH DG,LEE WM. Drug-induced acute liver failure:Results of a U. S. multicenter,prospective study[J].Hepatology,2010,52(6):2065-2076.

[35] ELSNER M,GULDBAKKE B,TIEDGE M,et al. Relative importance of transport and alkylation for pancreatic beta-cell toxicity of streptozotocin[J]. Diabetologia,2000,43(12):1528-1533.

[36] DUFRANE D,van STEENBERGHE M,GUIOT Y,et al. Streptozotocin-induced diabetes in large animals(pigs/primates):Role of GLUT2 transporter and beta-cell plasticity[J].Transplantation,2006,81(1):36-45.

[37] SUN Y,JIA Z,YANG G,et al. m PGES-2 deletion remarkably enhances liver injury in streptozotocin-treated mice via induction of GLUT2[J]. J Hepatol,2014,61(6):1328-1336.

[38] WANG H,ZHANG R,ZHU Y,et al. Microsomal prostaglandin E synthase 2 deficiency is resistant to acetaminophen-induced liver injury[J]. Arch Toxicol,2019,93(10):2863-2878.

[39] NAKATANI Y,HOKONOHARA Y,KAKUTA S,et al. Knockout mice lacking cPGES/p23,a constitutively expressed PGE2synthetic enzyme,are peri-natally lethal[J]. Biochem Biophys Res Commun,2007,362(2):387-392.

[40] LOVGREN AK,KOVAROVA M,KOLLER BH. cPGES/p23 is required for glucocorticoid receptor function and embryonic growth but not prostaglandin E2 synthesis[J]. Mol Cell Biol,2007,27(12):4416-4430.

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