葡萄糖转运子9及其遗传多态性在尿酸代谢和尿酸相关并发症中作用的研究进展
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摘要
当前国际和国内临床指南均推荐将尿酸控制在合理的水平。葡萄糖转运子9(GLUT9)是高效的尿酸转运蛋白,通过感知局部器官的尿酸水平,调控其他器官对尿酸代谢的调节,在不同病理生理条件下维持全身血尿酸水平平衡。同时,GLUT9的遗传多态性研究和分子学研究显示,GLUT9可直接或间接参与尿酸相关并发症的发生发展。除遗传多态性对GLUT9的影响外,多种内源性因子和外源性药物亦可影响GLUT9的表达和功能,调控尿酸。对GLUT9结构和功能的深入了解,对开发新型降尿酸药物,维持合理的血尿酸水平,控制尿酸相关并发症具有重要意义。
引文
[1]高尿酸血症相关疾病诊疗多学科共识专家组.中国高尿酸血症相关疾病诊疗多学科专家共识[J].中华内科杂志,2017,56:235-248.
[2]孙东霞,丁岩.尿酸与脑血管病及其高危因素相关性的研究进展[J].北京医学,2018,40:457-459.
[3]刘佳,王洁妤,李耘,等.不同程度血尿酸水平对老年人群认知功能损害的影响[J].北京医学,2017,39:810-814.
[4]张冰清,张昀,曾学军.尿酸转运蛋白是治疗高尿酸血症的新靶点[J].基础医学与临床,2014,34:1582-1585.
[5]Ruiz A,Gautschi I,Schild L,et al.Human mutations in SLC2A9(Glut9)affect transport capacity for urate[J].Front Physiol,2018,9:476.
[6]Mou LJ,Jiang LP,Hu Y.A novel homozygous GLUT9 mutation cause recurrent exercise-induced acute renal failure and posterior reversible encephalopathy syndrome[J].J Nephrol,2015,28:387-392.
[7]Preitner F,Bonny O,Laverrière A,et al.Glut9 is a major regulator of urate homeostasis and its genetic inactivation induces hyperuricosuria and urate nephropathy[J].Proc Natl Acad Sci U S A,2009,106:15501-15506.
[8]DeBosch BJ,Kluth O,Fujiwara H,et al.Early-onset metabolic syndrome in mice lacking the intestinal uric acid transporter SLC2A9[J].Nat Commun,2014,5:4642.
[9]K?ttgen A,Albrecht E,Teumer A,et al.Genome-wide association analyses identify 18 new loci associated with serum urate concentrations[J].Nat Genet,2013,45:145-154.
[10]Okada Y,Sim X,Go MJ,et al.Meta-analysis identifies multiple loci associated with kidney function-related traits in east Asian populations[J].Nat Genet,2012,44:904-909.
[11]Li Z,Zhou Z,Hou X,et al.Replication of gout/urate concentrations GWAS susceptibility loci associated with gout in a Han Chinese population[J].Sci Rep,2017,7:4094.
[12]Matsuo H,Yamamoto K,Nakaoka H,et al.Genome-wide association study of clinically defined gout identifies multiple risk loci and its association with clinical subtypes[J].Ann Rheum Dis,2016,75:652-659.
[13]张冰清,齐德光,张昀,等.痛风相关骨侵蚀的发生机制[J].北京医学,2015,37:981-983.
[14]Testa A,Mallamaci F,Spoto B,et al.Association of a polymorphism in a gene encoding a urate transporter with CKD progression[J].Clin J Am Soc Nephrol,2014,9:1059-1065.
[15]Kang DH.Hyperuricemia and progression of chronic kidney disease:role of phenotype transition of renal tubular and endothelial cells[J].Contrib Nephrol,2018,192:48-55.
[16]Choi YJ,Shin HS,Choi HS,et al.Uric acid induces fat accumulation via generation of endoplasmic reticulum stress and SREBP-1c activation in hepatocytes[J].Lab Invest,2014,94:1114-1125.
[17]Jia L,Xing J,Ding Y,et al.Hyperuricemia causes pancreatic b-cell death and dysfunction through NF-kB signaling pathway[J].PLoSOne,2013,8:e78284.
[18]Kanellis J,Watanabe S,Li JH,et al.Uric acid stimulates monocyte chemoattractant protein-1 production in vascular smooth muscle cells via mitogen-activated protein kinase and cyclooxygenase-2[J].Hypertension,2003,41:1287-1293.
[19]Keembiyehetty C,Augustin R,Carayannopoulos MO,et al.Mouse glucose transporter 9 splice variants are expressed in adult liver and kidney and are up-regulated in diabetes[J].Mol Endocrinol,2006,20:686-697.
[20]Ng HY,Lee YT,Kuo WH,et al.Alterations of renal epithelial glucose and uric acid transporters in fructose induced metabolic syndrome[J].Kidney Blood Press Res,2018,43:1822-1831.
[21]Evans SA,Doblado M,Chi MM,et al.Facilitative glucose transporter9 expression affects glucose sensing in pancreatic beta-cells[J].Endocrinology,2009,150:5302-5310.
[22]Houlihan LM,Wyatt ND,Harris SE,et al.Variation in the uric acid transporter gene(SLC2A9)and memory performance[J].Hum Mol Genet,2010,19:2321-2330.
[23]Facheris MF,Hicks AA,Minelli C,et al.Variation in the uric acid transporter gene SLC2A9 and its association with AAO of Parkinson's disease[J].J Mol Neurosci,2011,43:246-250.
[24]Uemura N,Murakami R,Chiba Y,et al.Immunoreactivity of urate transporters,GLUT9 and URAT1,is located in epithelial cells of the choroid plexus of human brains[J].Neurosci Lett,2017,659:99-103.
[25]Itahana Y,Han R,Barbier S,et al.The uric acid transporter SLC2A9is a direct target gene of the tumor suppressor p53 contributing to antioxidant defense[J].Oncogene,2015,34:1799-1810.
[26]Han X,Yang J,Li D,et al.Overexpression of uric acid transporter SLC2A9 inhibits proliferation of hepatocellular carcinoma cells[J].Oncol Res,2018,doi:10.3727/096504018X 15199489058224.[Epub ahead of print]
[27]Prestin K,Wolf S,Feldtmann R,et al.Transcriptional regulation of urate transportosome member SLC2A9 by nuclear receptor HNF4a[J].Am J Physiol Renal Physiol,2014,307:F1041-F1051.
[28]Mandal AK,Mercado A,Foster A,et al.Uricosuric targets of tranilast[J].Pharmacol Res Perspect,2017,5:e00291.
[29]Long W,Panwar P,Witkowska K,et al.Critical roles of two hydrophobic residues within human glucose transporter 9(hSLC2A9)in substrate selectivity and urate transport[J].J Biol Chem,2015,290:15292-15303.
[30]Long W,Panigrahi R,Panwar P,et al.Identification of key residues for urate specific transport in human glucose transporter 9(hSLC2A9)[J].Sci Rep,2017,7:41167.
[2]孙东霞,丁岩.尿酸与脑血管病及其高危因素相关性的研究进展[J].北京医学,2018,40:457-459.
[3]刘佳,王洁妤,李耘,等.不同程度血尿酸水平对老年人群认知功能损害的影响[J].北京医学,2017,39:810-814.
[4]张冰清,张昀,曾学军.尿酸转运蛋白是治疗高尿酸血症的新靶点[J].基础医学与临床,2014,34:1582-1585.
[5]Ruiz A,Gautschi I,Schild L,et al.Human mutations in SLC2A9(Glut9)affect transport capacity for urate[J].Front Physiol,2018,9:476.
[6]Mou LJ,Jiang LP,Hu Y.A novel homozygous GLUT9 mutation cause recurrent exercise-induced acute renal failure and posterior reversible encephalopathy syndrome[J].J Nephrol,2015,28:387-392.
[7]Preitner F,Bonny O,Laverrière A,et al.Glut9 is a major regulator of urate homeostasis and its genetic inactivation induces hyperuricosuria and urate nephropathy[J].Proc Natl Acad Sci U S A,2009,106:15501-15506.
[8]DeBosch BJ,Kluth O,Fujiwara H,et al.Early-onset metabolic syndrome in mice lacking the intestinal uric acid transporter SLC2A9[J].Nat Commun,2014,5:4642.
[9]K?ttgen A,Albrecht E,Teumer A,et al.Genome-wide association analyses identify 18 new loci associated with serum urate concentrations[J].Nat Genet,2013,45:145-154.
[10]Okada Y,Sim X,Go MJ,et al.Meta-analysis identifies multiple loci associated with kidney function-related traits in east Asian populations[J].Nat Genet,2012,44:904-909.
[11]Li Z,Zhou Z,Hou X,et al.Replication of gout/urate concentrations GWAS susceptibility loci associated with gout in a Han Chinese population[J].Sci Rep,2017,7:4094.
[12]Matsuo H,Yamamoto K,Nakaoka H,et al.Genome-wide association study of clinically defined gout identifies multiple risk loci and its association with clinical subtypes[J].Ann Rheum Dis,2016,75:652-659.
[13]张冰清,齐德光,张昀,等.痛风相关骨侵蚀的发生机制[J].北京医学,2015,37:981-983.
[14]Testa A,Mallamaci F,Spoto B,et al.Association of a polymorphism in a gene encoding a urate transporter with CKD progression[J].Clin J Am Soc Nephrol,2014,9:1059-1065.
[15]Kang DH.Hyperuricemia and progression of chronic kidney disease:role of phenotype transition of renal tubular and endothelial cells[J].Contrib Nephrol,2018,192:48-55.
[16]Choi YJ,Shin HS,Choi HS,et al.Uric acid induces fat accumulation via generation of endoplasmic reticulum stress and SREBP-1c activation in hepatocytes[J].Lab Invest,2014,94:1114-1125.
[17]Jia L,Xing J,Ding Y,et al.Hyperuricemia causes pancreatic b-cell death and dysfunction through NF-kB signaling pathway[J].PLoSOne,2013,8:e78284.
[18]Kanellis J,Watanabe S,Li JH,et al.Uric acid stimulates monocyte chemoattractant protein-1 production in vascular smooth muscle cells via mitogen-activated protein kinase and cyclooxygenase-2[J].Hypertension,2003,41:1287-1293.
[19]Keembiyehetty C,Augustin R,Carayannopoulos MO,et al.Mouse glucose transporter 9 splice variants are expressed in adult liver and kidney and are up-regulated in diabetes[J].Mol Endocrinol,2006,20:686-697.
[20]Ng HY,Lee YT,Kuo WH,et al.Alterations of renal epithelial glucose and uric acid transporters in fructose induced metabolic syndrome[J].Kidney Blood Press Res,2018,43:1822-1831.
[21]Evans SA,Doblado M,Chi MM,et al.Facilitative glucose transporter9 expression affects glucose sensing in pancreatic beta-cells[J].Endocrinology,2009,150:5302-5310.
[22]Houlihan LM,Wyatt ND,Harris SE,et al.Variation in the uric acid transporter gene(SLC2A9)and memory performance[J].Hum Mol Genet,2010,19:2321-2330.
[23]Facheris MF,Hicks AA,Minelli C,et al.Variation in the uric acid transporter gene SLC2A9 and its association with AAO of Parkinson's disease[J].J Mol Neurosci,2011,43:246-250.
[24]Uemura N,Murakami R,Chiba Y,et al.Immunoreactivity of urate transporters,GLUT9 and URAT1,is located in epithelial cells of the choroid plexus of human brains[J].Neurosci Lett,2017,659:99-103.
[25]Itahana Y,Han R,Barbier S,et al.The uric acid transporter SLC2A9is a direct target gene of the tumor suppressor p53 contributing to antioxidant defense[J].Oncogene,2015,34:1799-1810.
[26]Han X,Yang J,Li D,et al.Overexpression of uric acid transporter SLC2A9 inhibits proliferation of hepatocellular carcinoma cells[J].Oncol Res,2018,doi:10.3727/096504018X 15199489058224.[Epub ahead of print]
[27]Prestin K,Wolf S,Feldtmann R,et al.Transcriptional regulation of urate transportosome member SLC2A9 by nuclear receptor HNF4a[J].Am J Physiol Renal Physiol,2014,307:F1041-F1051.
[28]Mandal AK,Mercado A,Foster A,et al.Uricosuric targets of tranilast[J].Pharmacol Res Perspect,2017,5:e00291.
[29]Long W,Panwar P,Witkowska K,et al.Critical roles of two hydrophobic residues within human glucose transporter 9(hSLC2A9)in substrate selectivity and urate transport[J].J Biol Chem,2015,290:15292-15303.
[30]Long W,Panigrahi R,Panwar P,et al.Identification of key residues for urate specific transport in human glucose transporter 9(hSLC2A9)[J].Sci Rep,2017,7:41167.