水通道蛋白在肝纤维化及肝硬化进程中的作用

张强; 赵相轩; 孙巍; 次旦旺久; 郭启勇

doi:10.3969/j.issn.1001-5256.2016.06.041

水通道蛋白在肝纤维化及肝硬化进程中的作用

DOI: 10.3969/j.issn.1001-5256.2016.06.041

中国医科大学附属盛京医院放射科

基金项目:

国家自然科学基金资助项目(81471718);国家自然科学基金面上项目(31371425)；辽宁省自然科学基金(2013023056)；

详细信息

中图分类号: R575.2
计量
- 文章访问数: 1948
- HTML全文浏览量: 27
- PDF下载量: 434
- 被引次数: 0
出版历程
- 收稿日期: 2016-01-05
- 出版日期: 2016-06-20

Research advances in the role of aquaporins in liver fibrosis and liver cirrhosis

Research funding:

摘要

摘要: 肝硬化是各种慢性肝脏疾病的最终病理结果,多种细胞、细胞因子和微小RNA参与肝纤维化、肝硬化的发生和进展。肝纤维化与病理性血管生成相互依存、促进,肝纤维化动脉毛细血管增殖的病理生理机制尚不清楚,水通道蛋白不仅转运水而且促使新生血管形成。简述了水通道蛋白在肝胆系统表达及其生理生化特征,总结了水通道蛋白在肝纤维化、肝硬化进程中的作用,以期为水通道蛋白成为肝纤维化、肝硬化治疗靶点提供新的思路和指导。
- 肝硬化 /
- 水孔蛋白质类 /
- 综述
Abstract: Liver fibrosis is the final outcome of various chronic liver diseases,and various cells,cytokines,and miRNAs are involved in the development and progression of liver fibrosis and liver cirrhosis.Hepatic fibrosis and pathologic angiogenesis are interdependent processes and promote each other,but the physiopathological mechanism of arterial capillary proliferation in liver fibrosis remains unknown.Aquaporins not only transport water molecules,but also promote angiogenesis.This article briefly introduces the expression of aquaporins in the hepatobiliary system and their physiological and biochemical characteristics and summarizes the role of aquaporins in the progression of liver fibrosis and liver cirrhosis,in order to provide new thoughts and guidance for aquaporins as the target in the treatment of liver fibrosis and liver cirrhosis.
- liver cirrhosis /
- aquaporins /
- review

HTML全文

参考文献(46)

[1]DANCYGIER H,SCHIRMACHER P.Fibrogenic reaction[J].Clin Hepatology,2010,21(7):251-268.

[2]LIM YM,KIM WR.The global impact of hepatic fibrosis and end-stage liver disease[J].Clin Liver Dis,2008,12(4):733-746.

[3]ELPEK G.Angiogenesis and liver fibrosis[J].World J Hepatol,2015,7(3):377-391.

[4]AGRE P,SASAKI S,CHRISPEELS MJ.Aquaporins:a family of water channel proteins[J].Am J Physiol,1993,265(2):f461.

[5]IGUCHI H,ODA M,YAMAZAKI H,et al.Participation of aquaporin-1 in vascular changes and remodeling in cirrhotic liver[J].Med Mol Morphol,2013,46(3):123-132.

[6]YOKOMORI H,ODA M,YOSHIMURA K,et al.Aquaporin-1associated with hepatic arterial capillary proliferation on hepatic sinusoid in human cirrhotic liver[J].Liver Int,2011,31(10):1554-1564.

[7]YOKOMORI H,ODA M,YOSHIMURA K,et al.Aberrant expressions of aquaporin-1 in association with capillarized sinusoidal endothelial cells in cirrhotic rat liver[J].Med Mol Morphol,2010,43(1):6-12.

[8]BENGA G.Birth of water channel proteins-the aquaporins[J].Cell Biol Int,2003,27(9):701-709.

[9]XIN J,SUN TJ,ZHANG X,et al.Advances in aquaporin molecular targeted therapy and molecular targeted imaging[J].J Chin Clin Med Imaging,2014,25(11):807-810.(in Chinese)辛军,孙天娇,张新,等.水通道蛋白分子靶向治疗和分子靶向成像研究进展[J].中国临床医学影像杂志,2014,25(11):807-810.

[10]VERKMAN AS,HARA-CHIKUMA M,PAPADOPOULOS MC.Aquaporins---new players in cancer biology[J].J Mol Med(Berl),2008,86(5):523-529.

[11]PORTINCASA P,PALASCIANO G,SVELTO M,et al.Aquaporins in the hepatobiliary tract.which,where and what they do in health and disease[J].Eur J Clin Invest,2008,38(1):1-10.

[12]BENGA G.Water channel proteins(later called aquaporins)and relatives:past,present,and future[J].IUBMB Life,2009,61(2):112-133.

[13]LIU K,WANG GF,WU XJ,et al.The research progress in the physiology of aquaporins in the hepatobiliary system[J].Parenter Enteral Nutr,2012,5(19):316-318.(in Chinese)刘凯,王革非,吴性江,等.水通道蛋白在肝胆系统中的生理学研究进展[J].肠外与肠内营养,2012,5(19):316-318.

[14]LAKNER AM,WALLING TL,MCKILLOP IH,et al.Altered aquaporin expression and role in apoptosis during hepatic stellate cell activation[J].Liver Int,2011,31(1):42-51.

[15]CARRERAS FI,LEHMANN GL,FERRI D,et al.Defective hepatocyte aquaporin-8 expression and reduced canalicular membrane water permeability in estrogen-induced cholestasis[J].Am JPhysiol Gastrointest Liver Physiol,2007,292(3):905-912.

[16]van ERPECUM KJ,WANG DQ,MOSCHETTA A,et al.Gallbladder histopathology during murine gallstone formation:relation to motility and concentrating function[J].J Lipid Res,2006,47(1):32-41.

[17]IGUCHI H,ODA M,YAMAZAKI H,et al.Aquaporin-1 is associated with arterial capillary proliferation and hepatic sinusoidal transformation contributing to portal hypertension in primary biliary cirrhosis[J].Med Mol Morphol,2014,47(2):90-99.

[18]MOBASHERI A,MARPLES D.Expression of the AQP-1 water channel in normal human tissues:a semiquantitative study using tissue microarray technology[J].Am J Physiol Cell Physiol,2004,286(3):c529-c537.

[19]HUEBERT RC,VASDEV MM,SHERGILL U,et al.Aquaporin-1facilitates angiogenic invasion in the pathological neovasculature that accompanies cirrhosis[J].Hepatology,2010,52(1):238-248.

[20]ECHEVARRIA M,MUNOZ-CABELLO AM,SANCHEZ-SILVA R,et al.Development of cytosolic hypoxia and hypoxia-inducible factor stabilization are facilitated by aquaporin-1 expression[J].J Biol Chem,2007,822(41):30207-30215.

[21]REESE J,DAS SK,PARIA BC,et al.Global gene expression analysis to identify molecular markers of uterine receptivity and embryo implantation[J].J Biol Chem,2001,276(47):44137-44145.

[22]RUBANYI GM,JOHNS A,KAUSER K.Effect of estrogen on endothelial function and angiogenesis[J].Vascul Pharmacol,2002,38(2):89-98.

[23]CORTEZ-PINTO H,BAPTISTA A,CAMILO ME,et al.Nonalcoholic steatohepatitis---long-term follow-up study:comparison with alcoholic hepatitis in ambulatory and hospitalized patients[J].Dig Dis Sci,2003,48(10):1909-1913.

[24]ROJEK AM,SKOWRONSKI MT,FUCHTBAUER EM,et al.Defective glycerol metabolism in aquaporin 9(AQP9)knockout mice[J].Proc Natl Acad Sci U S A,2007,104(9):3609-3614.

[25]CARBREY JM,GORELICK-FELDMAN DA,KOZONO D,et al.Aquaglyceroporin AQP9:solute permeation and metabolic control of expression in liver[J].Proc Natl Acad Sci U S A,2003,100(5):2945-2950.

[26]HARA-CHIKUMA M,SOHARA E,RAI T,et al.Progressive adipocyte hypertrophy in aquaporin-7-deficient mice:adipocyte glycerol permeability as a novel regulator of fat accumulation[J].JBiol Chem,2005,280(16):15493-15496.

[27]QIU LW,GU LY,LYU L,et al.Expression of aquaglyceroporins in nonalcoholic hepatocyte steatosis and its significance[J].J Third Milit Med Univ,2012,34(7):622-626.(in Chinese)邱烈旺,顾陆昀,吕琳,等.水甘油通道蛋白在非酒精性脂肪变性肝细胞模型中的表达及意义[J].第三军医大学学报,2012,34(7):622-626.

[28]CHIAPPINI F,BARRIER A,SAFFROY R,et al.Exploration of global gene expression in human liver steatosis by high-density oligonucleotide microarray[J].Lab Invest,2006,86(2):154-165.

[29]ROSENGREN S,HENSON PM,WORTHEN GS.Migration-associated volume changes in neutrophils facilitate the migratory process in vitro[J].Am J Physiol,1994,267(6 Pt 1):c1623-c1632.

[30]HUEBERT RC,JAGAVELU K,HENDRICKSON HI,et al.Aquaporin-1 promotes angiogenesis,fibrosis,and portal hypertension through mechanisms dependent on osmotically sensitive microRNAs[J].Am JPathol,2011,179(4):1851-1860.

[31]ESTEVA-FONT C,BACCARO ME,FERNANDEZ-LLAMA P,et al.Aquaporin-1 and aquaporin-2 urinary excretion in cirrhosis:relationship with ascites and hepatorenal syndrome[J].Hepatology,2006,44(6):1555-1563.

[32]JONASSEN TE,CHRISTENSEN S,KWON TH,et al.Renal water handing in rats with decompensated liver cirrhosis[J].Am J Physiol Renal Physiol,2000,279(6):f1101-f1109.

[33]GEILSWIJK M,THOMSEN KL,PEDERSEN EB,et al.Urinary aquaporin-2 excretion before and after transjugular intrahepatic portosystemic shunt insertion for refractory ascites[J].Scand J Gastroenterol,2015,50(4):454-461.

[34]AGGARWAL S,KRAMER D,YONAS H,et al.Cerebral hemodynamic and metabolic changes in fulminant hepatic failure:a retrospective study[J].Hepatology,1994,19(1):80-87.

[35]RAMA RAO KV,CHEN M,SIMARD JM,et al.Increased aquaporin-4 expression in ammonia-treated cultured astrocytes[J].Neuroreport,2003,14(18):2379-2382.

[36]RAMA RAO KV,NORENBERG MD.Aquaporin-4 in hepatic encephalopathy[J].Metab Brain Dis,2007,22(3-4):265-275.

[37]MONZANI E,BAZZOTTI R,PEREGO C,et al.AQP1 is not only a water channel:it contributes to cell migration through Lin7/beta-catenin[J].PLo S One,2009,4(7):e6167.

[38]IWAKIRI Y.Endothelial dysfunction in the regulation of cirrhosis and portal hypertension[J].Liver Int,2012,32(2):199-213.

[39]KANEKO K,YAGUI K,TANAKA A,et al.Aquaporin 1 is required for hypoxia-inducible angiogenesis in human retinal vascular endothelial cells[J].Microvasc Res,2008,75(3):297-301.

[40]CLAPP C,MARTINEZ de la ESCALERA G.Aquaporin-1:a novel promoter of tumor angiogenesis[J].Trends Endocrinol Metab,2006,17(1):1-2.

[41]GARCIA F,KIERBEL A,LAROCCA MC,et al.The water channel aquaporin-8 is mainly intracellular in rat hepatocytes,and its plasma membrane insertion is stimulated by cyclic AMP[J].J Biol Chem,2001,276(15):12147-12152.

[42]RIBATTI D,RANIERI G,ANNESE T,et al.Aquaporins in cancer[J].Biochim Biophys Acta,2014,1840(5):1550-1553.

[43]HUBER VJ,TSUJITA M,NAKADA T.Aquaporins in drug discovery and pharmacotherapy[J].Mol Aspects Med,2012,33(5-6):691-703.

[44]HUBER VJ,TSUJITA M,NAKADA T.Identification of aquaporin4 inhibitors using in vitro and in silico methods[J].Bioorg Med Chem,2009,17(1):411-417.

[45]MA B,XIANG Y,MU SM,et al.Effects of acetazolamide and anordiol on osmotic water permeability in AQP1-cRNA injected xenopus oocyte[J].Acta Pharmacol Sin,2004,25(1):90-97.

[46]MIGLIATI E,MEURICE N,DUBOIS P,et al.Inhibition of aquaporin-1 and aquaporin-4 water permeability by a derivative of the loop diuretic bumetanide acting at an internal pore-occluding binding site[J].Mol Pharmacol,2009,76(1):105-112.

施引文献

资源附件(0)

访问统计