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中华肾病研究电子杂志 ›› 2016, Vol. 05 ›› Issue (04) : 177 -181. doi: 10.3877/cma.j.issn.2095-3216.2016.04.008

所属专题: 文献

综述

表观遗传修饰在糖尿病肾病发病机制中的作用研究进展
刘晓敏1, 董哲毅1, 陈香美1,()   
  1. 1. 100853 解放军总医院肾脏病科、解放军肾脏病研究所、肾脏疾病国家重点实验室、国家慢性肾病临床医学研究中心
  • 收稿日期:2016-05-06 出版日期:2016-08-28
  • 通信作者: 陈香美
  • 基金资助:
    973项目(2015CB553605); 国家自然科学基金(81473531,61471399,61001218); 解放军总医院科技创新苗圃基金(16KMM08); 解放军总医院临床科研扶持基金(2016FC-TSYS-1043)

Progress of research on the role of epigenetic modification in pathogenesis of diabetic nephropathy

Xiaomin Liu1, Zheyi Dong1, Xiangmei Chen1,()   

  1. 1. Department of Nephrology, Chinese PLA General Hospital, Chinese PLA Institute of Nephrology, State Key Laboratory of Kidney Diseases, National Clinical Research Center for Kidney Diseases. Beijing 100853, China
  • Received:2016-05-06 Published:2016-08-28
  • Corresponding author: Xiangmei Chen
  • About author:
    Corresponding author: Chen Xiangmei, Email:
引用本文:

刘晓敏, 董哲毅, 陈香美. 表观遗传修饰在糖尿病肾病发病机制中的作用研究进展[J]. 中华肾病研究电子杂志, 2016, 05(04): 177-181.

Xiaomin Liu, Zheyi Dong, Xiangmei Chen. Progress of research on the role of epigenetic modification in pathogenesis of diabetic nephropathy[J]. Chinese Journal of Kidney Disease Investigation(Electronic Edition), 2016, 05(04): 177-181.

"代谢记忆"现象是导致糖尿病并发症发病率持续增高的重要原因,其分子机制的研究主要聚焦在表观遗传修饰。表观遗传修饰在糖尿病肾病的纤维化、炎症、氧化应激、糖代谢及脂代谢紊乱等发病机制中有重要的作用。本文就该机制做一综述,并为进一步的分子研究、诊断及治疗提供新思路。

"Metabolic memory" phenomenon is an important reason that leads to the rising incidence of diabetes complications. Efforts to understand molecular mechanisms of the metabolic memory have been focused on the epigenetic modification. The epigenetic modification plays an important role in the pathogenesis of diabetic nephropathy, including fibrosis, inflammation, oxidative stress, and disorders of glucose metabolism and lipid metabolism, which was reviewed in this article, in order to provide new ideas for further molecular research, diagnosis, and treatment.

[1]
Guariguata L,Whiting DR,Hambleton I, et al. Global estimates of diabetes prevalence for 2013 and projections for 2035[J]. Diabetes Res Clin Pract, 2014, 103(2): 137-149.
[2]
Woroniecka KI,Park AS,Mohtat D, et al. Transcriptome analysis of human diabetic kidney disease[J]. Diabetes, 2011, 60(9): 2354-2369.
[3]
Rathmann W,Giani G. Global prevalence of diabetes: estimates for the year 2000 and projections for 2030[J]. Diabetes Care, 2004, 27(10): 2568-2569.
[4]
The Diabetes Control and Complications Trial Research Group. The effect of intensive treatment of diabetes on the development and progression of long-term complications in insulin-dependent diabetes mellitus[J]. N Engl J Med, 1993, 329(14): 977-986.
[5]
UK Prospective Diabetes Study (UKPDS) Group. Intensive blood-glucose control with sulphonylureas or insulin compared with conventional treatment and risk of complications in patients with type 2 diabetes (UKPDS 33)[J]. Lancet, 1998, 352(9131): 837-853.
[6]
Holman RR,Paul SK,Bethel MA, et al. 10-year follow-up of intensive glucose control in type 2 diabetes[J]. N Engl J Med, 2008, 359(15): 1577-1589.
[7]
Skinner MK. Environmental epigenomics and disease susceptibility[J]. EMBO Rep, 2011, 12(7): 620-622.
[8]
Cantone I,Fisher AG. Epigenetic programming and reprogramming during development[J]. Nat Struct Mol Biol, 2013, 20(3): 282-289.
[9]
Saetrom P,Snove OJ,Rossi JJ. Epigenetics and microRNAs[J]. Pediatr Res, 2007, 61(5 Pt 2): 17R-23R.
[10]
Campbell SA,Hoffman BG. Chromatin regulators in pancreas development and diabetes[J]. Trends Endocrinol Metab, 2016, 27(3): 142-152.
[11]
Butler JS,Koutelou E,Schibler AC, et al. Histone-modifying enzymes: regulators of developmental decisions and drivers of human disease[J]. Epigenomics, 2012, 4(2): 163-177.
[12]
Advani A,Huang Q,Thai K, et al. Long-term administration of the histone deacetylase inhibitor vorinostat attenuates renal injury in experimental diabetes through an endothelial nitric oxide synthase-dependent mechanism[J]. Am J Pathol, 2011, 178(5): 2205-2214.
[13]
Zhou J,Peng R,Li T, et al. A potentially functional polymorphism in the regulatory region of let-7a-2 is associated with an increased risk for diabetic nephropathy[J]. Gene, 2013, 527(2): 456-461.
[14]
Thomas MC. Advanced glycation end products[J]. Contrib Nephrol, 2011, 170: 66-74.
[15]
Jirtle RL,Skinner MK. Environmental epigenomics and disease susceptibility[J]. Nat Rev Genet, 2007, 8(4): 253-262.
[16]
Toperoff G,Kark JD,Aran D, et al. Premature aging of leukocyte DNA methylation is associated with type 2 diabetes prevalence[J]. Clin Epigenetics, 2015, 7(1): 35.
[17]
Vanderjagt TA,Neugebauer MH,Morgan M, et al. Epigenetic profiles of pre-diabetes transitioning to type 2 diabetes and nephropathy[J]. World J Diabetes, 2015, 6(9): 1113-1121.
[18]
Ren F,Tang L,Cai Y, et al. Meta-analysis: the efficacy and safety of combined treatment with ARB and ACEI on diabetic nephropathy[J]. Ren Fail, 2015, 37(4): 548-561.
[19]
Li LM,Hou DX,Guo YL, et al. Role of microRNA-214-targeting phosphatase and tensin homolog in advanced glycation end product-induced apoptosis delay in monocytes[J]. J Immunol, 2011, 186(4): 2552-2560.
[20]
Xiao L,Wang M,Yang S, et al. A glimpse of the pathogenetic mechanisms of Wnt/beta-catenin signaling in diabetic nephropathy[J]. Biomed Res Int, 2013, 2013: 987064.
[21]
Bechtel W,Mcgoohan S,Zeisberg EM, et al. Methylation determines fibroblast activation and fibrogenesis in the kidney[J]. Nat Med, 2010, 16(5): 544-550.
[22]
Ross S,Cheung E,Petrakis TG, et al. Smads orchestrate specific histone modifications and chromatin remodeling to activate transcription[J]. EMBO J, 2006, 25(19): 4490-4502.
[23]
Yuan H,Reddy MA,Sun G, et al. Involvement of p300/CBP and epigenetic histone acetylation in TGF-beta1-mediated gene transcription in mesangial cells[J]. Am J Physiol Renal Physiol, 2013, 304(5): F601-F613.
[24]
Yuan H,Reddy MA,Sun G, et al. Involvement of p300/CBP and epigenetic histone acetylation in TGF-beta1-mediated gene transcription in mesangial cells[J]. Am J Physiol Renal Physiol, 2013, 304(5): F601-F613.
[25]
Sun G,Reddy MA,Yuan H, et al. Epigenetic histone methylation modulates fibrotic gene expression[J]. J Am Soc Nephrol, 2010, 21(12): 2069-2080.
[26]
Khan S,Jena G,Tikoo K. Sodium valproate ameliorates diabetes-induced fibrosis and renal damage by the inhibition of histone deacetylases in diabetic rat[J]. Exp Mol Pathol, 2015, 98(2): 230-239.
[27]
Kato M,Zhang J,Wang M, et al. MicroRNA-192 in diabetic kidney glomeruli and its function in TGF-beta-induced collagen expression via inhibition of E-box repressors[J]. Proc Natl Acad Sci USA, 2007, 104(9): 3432-3437.
[28]
Putta S,Lanting L,Sun G, et al. Inhibiting microRNA-192 ameliorates renal fibrosis in diabetic nephropathy[J]. J Am Soc Nephrol, 2012, 23(3): 458-469.
[29]
Wang Q,Wang Y,Minto AW, 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.
[30]
Krupa A,Jenkins R,Luo DD, et al. Loss of microRNA-192 promotes fibrogenesis in diabetic nephropathy[J]. J Am Soc Nephrol, 2010, 21(3): 438-447.
[31]
Wang B,Koh P,Winbanks C, et al. miR-200a prevents renal fibrogenesis through repression of TGF-beta2 expression[J]. Diabetes, 2011, 60(1): 280-287.
[32]
Wang B,Komers R,Carew R, et al. Suppression of microRNA-29 expression by TGF-beta1 promotes collagen expression and renal fibrosis[J]. J Am Soc Nephrol, 2012, 23(2): 252-265.
[33]
Wang B,Jha JC,Hagiwara S, et al. Transforming growth factor-beta1-mediated renal fibrosis is dependent on the regulation of transforming growth factor receptor 1 expression by let-7b[J]. Kidney Int, 2014, 85(2): 352-361.
[34]
Brennan EP,Nolan KA,Borgeson E, et al. Lipoxins attenuate renal fibrosis by inducing let-7c and suppressing TGFbetaR1[J]. J Am Soc Nephrol, 2013, 24(4): 627-637.
[35]
Alvarez ML,Distefano JK. Functional characterization of the plasmacytoma variant translocation 1 gene (PVT1) in diabetic nephropathy[J]. PLoS One, 2011, 6(4): e18671.
[36]
Alvarez ML,Khosroheidari M,Eddy E, et al. Role of microRNA 1207-5P and its host gene, the long non-coding RNA Pvt1, as mediators of extracellular matrix accumulation in the kidney: implications for diabetic nephropathy[J]. PLoS One, 2013, 8(10): e77468.
[37]
Simar D,Versteyhe S,Donkin I, et al. DNA methylation is altered in B and NK lymphocytes in obese and type 2 diabetic human[J]. Metabolism, 2014, 63(9): 1188-1197.
[38]
Zhao J,Goldberg J,Bremner JD, et al. Global DNA methylation is associated with insulin resistance: a monozygotic twin study[J]. Diabetes, 2012, 61(2): 542-546.
[39]
Reddy MA,Natarajan R. Epigenetic mechanisms in diabetic vascular complications[J]. Cardiovasc Res, 2011, 90(3): 421-429.
[40]
Shanmugam N,Reddy MA,Guha M, et al. High glucose-induced expression of proinflammatory cytokine and chemokine genes in monocytic cells[J]. Diabetes, 2003, 52(5): 1256-1264.
[41]
Miao F,Gonzalo IG,Lanting L, et al. In vivo chromatin remodeling events leading to inflammatory gene transcription under diabetic conditions[J]. J Biol Chem, 2004, 279(17): 18091-18097.
[42]
Miao F,Chen Z,Genuth S, et al. Evaluating the role of epigenetic histone modifications in the metabolic memory of type 1 diabetes[J]. Diabetes, 2014, 63(5): 1748-1762.
[43]
Villeneuve LM,Reddy MA,Lanting LL, et al. Epigenetic histone H3 lysine 9 methylation in metabolic memory and inflammatory phenotype of vascular smooth muscle cells in diabetes[J]. Proc Natl Acad Sci USA, 2008, 105(26): 9047-9052.
[44]
Huang Y,Liu Y,Li L, et al. Involvement of inflammation-related miR-155 and miR-146a in diabetic nephropathy: implications for glomerular endothelial injury[J]. BMC Nephrol, 2014, 15: 142.
[45]
Zhong Q,Kowluru RA. Regulation of matrix metalloproteinase-9 by epigenetic modifications and the development of diabetic retinopathy[J]. Diabetes, 2013, 62(7): 2559-2568.
[46]
El-Osta A,Brasacchio D,Yao D, et al. Transient high glucose causes persistent epigenetic changes and altered gene expression during subsequent normoglycemia[J]. J Exp Med, 2008, 205(10): 2409-2417.
[47]
Brownlee M. Biochemistry and molecular cell biology of diabetic complications[J]. Nature, 2001, 414(6865): 813-820.
[48]
Zhong Q,Kowluru RA. Epigenetic modification of Sod2 in the development of diabetic retinopathy and in the metabolic memory: role of histone methylation[J]. Invest Ophthalmol Vis Sci, 2013, 54(1): 244-250.
[49]
Bock F,Shahzad K,Wang H, et al. Activated protein C ameliorates diabetic nephropathy by epigenetically inhibiting the redox enzyme p66Shc[J]. Proc Natl Acad Sci USA, 2013, 110(2): 648-653.
[50]
Siddiqi FS,Majumder S,Thai K, et al. The histone methyltransferase enzyme enhancer of zeste homolog 2 protects against podocyte oxidative stress and renal injury in diabetes[J]. J Am Soc Nephrol, 2016, 27(7): 2021-2034.
[51]
Chau BN,Xin C,Hartner J, et al. MicroRNA-21 promotes fibrosis of the kidney by silencing metabolic pathways[J]. Sci Transl Med, 2012, 4(121): 118r-121r.
[52]
Thallas-Bonke V,Jandeleit-Dahm KA,Cooper ME. Nox-4 and progressive kidney disease[J]. Curr Opin Nephrol Hypertens, 2015, 24(1): 74-80.
[53]
Yang BT,Dayeh TA,Kirkpatrick CL, et al. Insulin promoter DNA methylation correlates negatively with insulin gene expression and positively with HbA(1c) levels in human pancreatic islets[J]. Diabetologia, 2011, 54(2): 360-367.
[54]
Barres R,Osler ME,Yan J, et al. Non-CpG methylation of the PGC-1alpha promoter through DNMT3B controls mitochondrial density[J]. Cell Metab, 2009, 10(3): 189-198.
[55]
Kumar S,Pamulapati H,Tikoo K. Fatty acid induced metabolic memory involves alterations in renal histone H3K36me2 and H3K27me3[J]. Mol Cell Endocrinol, 2016, 422: 233-242.
[56]
Gupta J,Kumar S,Li J, et al. Histone H3 lysine 4 monomethylation (H3K4me1) and H3 lysine 9 monomethylation (H3K9me1): distribution and their association in regulating gene expression under hyperglycaemic/hyperinsulinemic conditions in 3T3 cells[J]. Biochimie, 2012, 94(12): 2656-2664.
[57]
Wu H,Min J,Lunin VV, et al. Structural biology of human H3K9 methyltransferases[J]. PLoS One, 2010, 5(1): e8570.
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