糖尿病肾病中转化生长因子β_1/Sma和Mad相关蛋白信号通路的作用及其相关药物研究进展被引量：43

Effect of transforming growth factor beta 1/Sma- and Mad-related protein signal pathwayin diabetic nephropathy and related drugs:a review

下载PDF

导出

摘要转化生长因子β1(TGF-β1)参与糖尿病肾病(DN)的进程已作为临床慢性肾病进展的重要生物学标志物和治疗靶标。Sma和Mad相关蛋白(Smad)是TGF-β家族下游信号转导蛋白,TGF-β1与受体结合激活Smad2和Smad3,上调细胞核内结缔组织生长因子的转录,Smad3促进系膜细胞增生、细胞外基质积聚和细胞上皮间质转化,导致肾纤维化;Smad2和Smad7则起着负向调控作用,抑制肾纤维化。TGF-β1特异性抑制剂(SB431542等)具有抗肾纤维化作用,大多处在临床前研究阶段,已上市的对DN有一定疗效的药物如苯那普利、阿托伐他汀、氯沙坦和吡非尼酮等可抑制TGF-β1表达,雷公藤、冬虫夏草和小檗碱也通过降低TGF-β1水平延缓DN进程。本文就近年来TGF-β1/Smad信号通路及其防治药物在DN中的研究进展进行综述。 Transforming growth factor-β1（TGF-β1）has become an important biological marker and therapeutic target of clinical progression of chronic kidney diseases. Sma- and Mad-related protein（Smad）is a downstream signal transduction protein of the TGF-β family. TGF-β1activates Smad2 and Smad3 before increasing the transcription of connective tissue growth factors in the nucleus. Smad3 promotes mesangial cel proliferation,extracel ular matrix accumulation,epithelial-mesenchymal transition,leading to renal fibrosis. However,Smad2 and Smad7 play a negative regulatory role by inhibiting renal fibrosis. TGF- β1specific inhibitor（SB431542,etc.）has antifibrosis effect,most of which is in the preclinical stage. The drugs on the market that are effective for DN,such as benzodiazepines,atorvastatin,losartan,and pirfenidone,can inhibit the expression of TGF-β1,while tripterygium wilfordii,cordyceps sinensis,and berberine can delay the process of diabetic nephropathy by reducing TGF-β1levels.

作者贾会玉李中南陈光亮

机构地区安徽中医药大学中西医结合临床学院安徽中医药大学第一附属医院

出处《中国药理学与毒理学杂志》 CAS CSCD 北大核心 2016年第3期266-271,共6页 Chinese Journal of Pharmacology and Toxicology

基金国家中医临床研究基地业务建设科研专项项目(JDZX2012004)~~

关键词糖尿病肾病转化生长因子β1 信号通路药物 diabetic nephropathy transforming growth factor-β1 signaling pathway drugs

分类号 R587.2 [医药卫生—内分泌] R692.9 [医药卫生—泌尿科学]

引文网络
相关文献

参考文献39

1Lan HY.Diverse roles of TGF-β/Smads in renal fibrosis and inflammation[J].Int J Biol Sci,2011,7(7):1056-1067.
2Lee SB,Kanasaki K,Kalluri R.Circulating TGFbeta1 as a reliable biomarker for chronic kidney disease progression in the African-American population[J].Kidney Int,2009,76(1):10-12.
3Hills CE,Squires PE.The role of TGF-βand epithelial-to mesenchymal transition in diabetic nephropathy[J].Cytokine Growth Factor Rev,2011,22(3):131-139.
4She S,Liu W,Li T,Hong Y.Effects of puerarin in STZ-induced diabetic rats by oxidative stress and the TGF-β1/Smad2 pathway[J].Food Funct,2014,5(5):944-950.
5Hills CE,Squires PE.TGF-beta1-induced epithelialto-mesenchymal transition and therapeutic intervention in diabetic nephropathy[J].Am J Nephrol,2010,31(1):68-74.
6Brennan EP,Morine MJ,Walsh DW,Roxburgh SA,Lindenmeyer MT,Brazil DP,et al.Next-generation sequencing identifies TGF-β1-associated gene expression profiles in renal epithelial cells reiterated in human diabetic nephropathy[J].Biochem Biophys Acta,2012,1822(4):589-599.
7Lan HY,Chung AC.Transforming growth factor-βand Smads[J].Contrib Nephrol,2011,170:75-82.
8Meng XM,Tang PM,Li J,Lan HY.TGF-β/Smad signaling in renal fibrosis[J].Front Physiol,2015,6:82.
9Chung AC,Zhang H,Kong YZ,Tan JJ,Huang XR,Kopp JB,et al.Advanced glycation endproducts induce tubular CTGF via TGF-beta-independent Smad3 signaling[J].J Am Soc Nephrol,2010,21(2):249-260.
10Zhou L,Fu P,Huang XR,Liu F,Chung AC,Lai KN,et al.Mechanism of chronic aristolochic acid nephropathy:role of Smad3[J].Am J Physiol Renal Physiol,2010,298(4):F1006-1017.