糖尿病肾病(diabetic nephropathy,DN)是糖尿病患者最常见的微血管并发症之一,也是终末期肾病的重要病因,肾小球硬化是本病的特征,但其发病机制仍不清楚.因此,深入认识糖尿病肾病的发病机制,干扰其发病环节,不仅可以减轻患者的痛苦,而且对减轻国家在卫生经济费用方面的负担也有重要意义.微小核糖核酸(microRNA,miRNA)是一类非编码的微小RNA,近些年有研究发现miRNA在基因中的调控作用,可能成为糖尿病肾病的一种新的诊断标志物和治疗靶点.在本文中作者对与糖尿病肾病有关的miRNA的作用作一综述.

[1] 张迎建,李文超,杨红.microRNA在预防医学中的研究进展[J].东南大学学报:医学版,2013,32(5):606-611.
[2] MITCHELL P S,PARKIN R K,KROH E M et al.Circulating microRNAs as stable blood-based markers for cancer detection[J].Proc Natl Acad Sci US A,2008,105(30):10513-10518.
[3] NG E K,CHONG W W,JIN H,et al.Differential expression of microRNAs in plasma of patients with colorectal cancer:a potential marker for colorectal cancer screening[J].Gut,2009,58(10):1375-1381.
[4] RUSSO G,GIORDANO A.miRNAs:from biogenesis to networks[J].Methods Mol Biol,2009,563:303-352.
[5] LEWIS B P,BURGE C R,BARTEL D P.Conserverd seed pairing,often flanked by adenosines,indicates that thousands of human genes are microRNA target[J].Cell,2005,120(1):15-20.
[6] KUEHBACHER A,UTBICH C,ZEIHER A M,et al.Role of Dicer and Drosha for endothelial microRNA expression and angiogenesis[J].Circ Res,2007,101(1):59-68.
[7] YAMAGISHI S,FUKAMI K,UEDA S,et al.Molecular mechanisms of diabetic nephropathy and its therapeutic intervention[J].Curr Drug Targets,2007,8(8):952-959.
[8] QIAN Y,FELDMAN E,PENNATHUR S,et al.From fibrosis to sclerosis::mechanisms of glomerulosclerosis in diabetic nephropathy[J].Diabetes,2008,57(6):1439-1445.
[9] KATO M,PARK J T,NATARAJAN R.MicroRNAs and the glomerulus[J].Exp Cell Res,2012,318(9):993-1000.
[10] KATO M,ZHANG J,WANG M,et al.MicroRNA-192 in diabetic kidney glomeruli and its function in TGF-β-induced collagen expression via inhibition of E-box repressors[J].Proc Natl Acad Sci USA,2007,104(9),3432-3437.
[11] KATOL M,ARCEL L,WANG M,et al.A microRNA circuit mediates transforming growth factor-b1 autotegulation in renal glomerular mesangial cells[J].Kideny Int,2011,80(4):358-368.
[12] KATO M,PUTTA S,WANG M,et al.TGF-β activates Akt kinase through a microRNA-dependent amplifying circuit targeting PTEN[J].Nat Cell Biol,2009,11(7):881-889.
[13] WANG Q,WANG Y,MINTO A W,et al.MicroRNA-377 is up-regulated and can lead to increased fibronectin production in diabetic nephropathy[J].FASEB J,2008,22(12):4126-4135.
[14] HE F,PENG F,XIA X,et al.MiR-135a promotes renal fibrosis in diabetic nephropathy by regulating TRPC1[J].Diabetologia,2014 57(8):1726-1736.
[15] ZHANG Z,PENG H,CHEN J,et al.MicroRNA-21 protects from mesangial cell proliferation induced by diabetic nephropathy in db/db mice[J].FEBS Lett,2009,583(12):2009-2014.
[16] SHI S,YU L,CHIU C,et al.Podocyte-selective deletion of dicer induces proteinuria and glomerulosclerosis[J].Am Soc Nephrio,2008,19(11):2159-2169.
[17] HO J,NG K U,ROSEN S,et al.Podocyte-specific loss of functional microRNAs leads to rapid glomerular and tubular injury[J].Am Soc Nephrio,2008,19(11):2069-2075.
[18] 盖维,戴春,吕昌云.骨髓间充质干细胞对糖尿病肾病大鼠肾脏podocin表达的影响[J].现代医学,2014,42(10):1121-1126.
[19] HARVEY S J,JARAD G,CUNNINGHAM J,et al.Podocyte-specific deletion of Dicer alters cytoskeletal dynamics and causes glomerular disease[J].Am Soe Nephrol,2008,19(11):2150-2158.
[20] DUISTERS R F,TIJSEN A J,SCHMEN B,et al.MiR-133 and miR-30 regulate connective tissue growth factor:implications for a role of microRNAs in myocardial matrix remodelling[J].Cire Res,2009,104(2):170-178.
[21] LONG J,WANG Y,WANG W,et al.Identification of microRNA-93 as a novel regulator of vascular endothelial growth factor in hyperglycemic conditions[J].Biol Chem,2010,285(30):23457-23465.
[22] CAREW R M,WANG B,KANTHARIDIS P.The role of EMT in renal fibrosis[J].Cell Tissue Res,2012,347(1):103-116.
[23] 张飞飞,谭若云,熊明霞,等.高糖通过转化生长因子β1-Smad信号传递途径诱导肾小管上皮细胞转分化[J].中华肾脏病杂志,2008,24(3):174-178.
[24] WANG B,KOH P,WINBANKS C,et al.miR-200a Prevents renal fibrogenesis through repression of TGF-β2 expression[J].Diabetes,2011,60(1):280-287.
[25] WANG B,HERMAN-EDELSTEIN M,KOH P,et al.E-cadherin expression is regulated by miR-192/215 by a mechanism that is independent of the profibrotic effects of transforming growth factor-beta[J].Diabetes,2010,59(7):1794-1802.
[26] KRIEGEL A J,FANG Y,LIU Y,et al.MicroRNA-target pairs in human renal epithelial cells treated with transforming growth factor beta l:a novel role of miR-382[J].Nucleic Acids Res,2010,38(22):8338-8347.