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Journal of Diabetes Research
Volume 2016 (2016), Article ID 7934504, 23 pages
http://dx.doi.org/10.1155/2016/7934504
Review Article

A Systems Biology Overview on Human Diabetic Nephropathy: From Genetic Susceptibility to Post-Transcriptional and Post-Translational Modifications

1Division of Nephrology, Department of Emergency and Organ Transplantation, University of Bari, 70124 Bari, Italy
2Division of Cardiology and Cardiac Rehabilitation, “S. Maugeri” Foundation, IRCCS, Institute of Cassano Murge, 70020 Cassano delle Murge, Italy
3Molecular Medicine Center, Section of Nephrology, Department of Medical and Surgical Sciences, University of Foggia, 71122 Foggia, Italy

Received 29 May 2015; Revised 16 August 2015; Accepted 10 September 2015

Academic Editor: Shirong Zheng

Copyright © 2016 Francesca Conserva et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Linked References

  1. T. H. Hostetter, H. G. Rennke, and B. M. Brenner, “The case for intrarenal hypertension in the initiation and progression of diabetic and other glomerulopathies,” The American Journal of Medicine, vol. 72, no. 3, pp. 375–380, 1982. View at Publisher · View at Google Scholar · View at Scopus
  2. Y. S. Kanwar, L. Sun, P. Xie, F.-Y. Liu, and S. Chen, “A glimpse of various pathogenetic mechanisms of diabetic nephropathy,” Annual Review of Pathology: Mechanisms of Disease, vol. 6, pp. 395–423, 2011. View at Publisher · View at Google Scholar · View at Scopus
  3. M. Brownlee, “The pathobiology of diabetic complications: a unifying mechanism,” Diabetes, vol. 54, no. 6, pp. 1615–1625, 2005. View at Publisher · View at Google Scholar · View at Scopus
  4. H. S. Lee, “Pathogenic role of TGF-beta in the progression of podocyte diseases,” Histology and Histopathology, vol. 26, no. 1, pp. 107–116, 2011. View at Google Scholar · View at Scopus
  5. H. H. Parving, B. Oxenbøll, P. A. Svendsen, J. S. Christiansen, and A. R. Andersen, “Early detection of patients at risk of developing diabetic nephropathy. A longitudinal study of urinary albumin excretion,” Acta Endocrinologica (Copenhagen), vol. 100, no. 4, pp. 550–555, 1982. View at Google Scholar · View at Scopus
  6. G. C. Viberti, R. J. Jarrett, U. Mahmud, R. D. Hill, A. Argyropoulos, and H. Keen, “Microalbuminuria as a predictor of clinical nephropathy in insulin-dependent diabetes mellitus,” The Lancet, vol. 319, no. 8287, pp. 1430–1432, 1982. View at Publisher · View at Google Scholar · View at Scopus
  7. G. Mazzucco, T. Bertani, M. Fortunato et al., “Different patterns of renal damage in type 2 diabetes mellitus: a multicentric study on 393 biopsies,” American Journal of Kidney Diseases, vol. 39, no. 4, pp. 713–720, 2002. View at Publisher · View at Google Scholar · View at Scopus
  8. K. O. Alsaad and A. M. Herzenberg, “Distinguishing diabetic nephropathy from other causes of glomerulosclerosis: an update,” Journal of Clinical Pathology, vol. 60, no. 1, pp. 18–26, 2007. View at Publisher · View at Google Scholar · View at Scopus
  9. T. W. C. Tervaert, A. L. Mooyaart, K. Amann et al., “Pathologic classification of diabetic nephropathy,” Journal of the American Society of Nephrology, vol. 21, no. 4, pp. 556–563, 2010. View at Publisher · View at Google Scholar
  10. F. C. Brosius III, C. E. Alpers, E. P. Bottinger et al., “Mouse models of diabetic nephropathy,” Journal of the American Society of Nephrology, vol. 20, no. 12, pp. 2503–2512, 2009. View at Publisher · View at Google Scholar
  11. D. W. Bowden, C. J. Colicigno, C. D. Langefeld et al., “A genome scan for diabetic nephropathy in African Americans,” Kidney International, vol. 66, no. 4, pp. 1517–1526, 2004. View at Publisher · View at Google Scholar · View at Scopus
  12. I. Vardarli, L. J. Baier, R. L. Hanson et al., “Gene for susceptibility to diabetic nephropathy in type 2 diabetes maps to 18q22.3-23,” Kidney International, vol. 62, no. 6, pp. 2176–2183, 2002. View at Publisher · View at Google Scholar · View at Scopus
  13. N. D. Palmer, M. C. Y. Ng, P. J. Hicks et al., “Evaluation of candidate nephropathy susceptibility genes in a genome-wide association study of African American diabetic kidney disease,” PLoS ONE, vol. 9, no. 2, Article ID e88273, 2014. View at Publisher · View at Google Scholar · View at Scopus
  14. C. W. McDonough, N. D. Palmer, P. J. Hicks et al., “A genome-wide association study for diabetic nephropathy genes in African Americans,” Kidney International, vol. 79, no. 5, pp. 563–572, 2011. View at Publisher · View at Google Scholar · View at Scopus
  15. B. Janssen, D. Hohenadel, P. Brinkkoetter et al., “Carnosine as a protective factor in diabetic nephropathy: association with a leucine repeat of the carnosinase gene CNDP1,” Diabetes, vol. 54, no. 8, pp. 2320–2327, 2005. View at Publisher · View at Google Scholar · View at Scopus
  16. A. L. Mooyaart, E. J. J. Valk, L. A. Van Es et al., “Genetic associations in diabetic nephropathy: a meta-analysis,” Diabetologia, vol. 54, no. 3, pp. 544–553, 2011. View at Publisher · View at Google Scholar · View at Scopus
  17. J.-M. Zhu, B. Wang, J. Li et al., “D18S880 microsatellite polymorphism of carnosinase gene and diabetic nephropathy: a meta-analysis,” Genetic Testing and Molecular Biomarkers, vol. 17, no. 4, pp. 289–294, 2013. View at Publisher · View at Google Scholar · View at Scopus
  18. M. G. Pezzolesi, P. Katavetin, M. Kure et al., “Confirmation of genetic associations at ELMO1 in the GoKinD collection supports its role as a susceptibility gene in diabetic nephropathy,” Diabetes, vol. 58, no. 11, pp. 2698–2702, 2009. View at Publisher · View at Google Scholar · View at Scopus
  19. A. Shimazaki, Y. Kawamura, A. Kanazawa et al., “Genetic variations in the gene encoding ELMO1 are associated with susceptibility to diabetic nephropathy,” Diabetes, vol. 54, no. 4, pp. 1171–1178, 2005. View at Publisher · View at Google Scholar · View at Scopus
  20. B. I. Freedman, C. D. Langefeld, L. Lu et al., “Differential effects of MYH9 and APOL1 risk variants on FRMD3 association with diabetic ESRD in African Americans,” PLoS Genetics, vol. 7, no. 6, Article ID e1002150, 2011. View at Publisher · View at Google Scholar · View at Scopus
  21. M. G. Pezzolesi, J. Jeong, A. M. Smiles et al., “Family-based association analysis confirms the role of the chromosome 9q21.32 locus in the susceptibility of diabetic nephropathy,” PLoS ONE, vol. 8, no. 3, Article ID e60301, 2013. View at Publisher · View at Google Scholar · View at Scopus
  22. R. L. Hanson, D. W. Craig, M. P. Millis et al., “Identification of PVT1 as a candidate gene for end-stage renal disease in type 2 diabetes using a pooling-based genome-wide single nucleotide polymorphism association study,” Diabetes, vol. 56, no. 4, pp. 975–983, 2007. View at Publisher · View at Google Scholar · View at Scopus
  23. M. P. Millis, D. Bowen, C. Kingsley, R. M. Watanabe, and J. K. Wolford, “Variants in the plasmacytoma variant translocation gene (PVT1) are associated with end-stage renal disease attributed to type 1 diabetes,” Diabetes, vol. 56, no. 12, pp. 3027–3032, 2007. View at Publisher · View at Google Scholar · View at Scopus
  24. M. Herman-Edelstein, P. Scherzer, A. Tobar, M. Levi, and U. Gafter, “Altered renal lipid metabolism and renal lipid accumulation in human diabetic nephropathy,” Journal of Lipid Research, vol. 55, no. 3, pp. 561–572, 2014. View at Publisher · View at Google Scholar · View at Scopus
  25. T. Konoshita, S. Wakahara, S. Mizuno et al., “Tissue gene expression of renin-angiotensin system in human type 2 diabetic nephropathy,” Diabetes Care, vol. 29, no. 4, pp. 848–852, 2006. View at Publisher · View at Google Scholar · View at Scopus
  26. H. N. Reich, G. Y. Oudit, J. M. Penninger, J. W. Scholey, and A. M. Herzenberg, “Decreased glomerular and tubular expression of ACE2 in patients with type 2 diabetes and kidney disease,” Kidney International, vol. 74, no. 12, pp. 1610–1616, 2008. View at Publisher · View at Google Scholar · View at Scopus
  27. M. Zheng, L.-L. Lv, Y.-H. Cao et al., “A pilot trial assessing urinary gene expression profiling with an mRNA array for diabetic nephropathy,” PLoS ONE, vol. 7, no. 5, Article ID e34824, 2012. View at Publisher · View at Google Scholar · View at Scopus
  28. G. Wang, F. M.-M. Lai, K.-B. Lai, K.-M. Chow, K.-T. P. Li, and C.-C. Szeto, “Messenger RNA expression of podocyte-associated molecules in the urinary sediment of patients with diabetic nephropathy,” Nephron—Clinical Practice, vol. 106, no. 4, pp. c169–c179, 2007. View at Publisher · View at Google Scholar · View at Scopus
  29. M. Zheng, L.-L. Lv, J. Ni et al., “Urinary podocyte-associated mRNA profile in various stages of diabetic nephropathy,” PLoS ONE, vol. 6, no. 5, Article ID e20431, 2011. View at Publisher · View at Google Scholar · View at Scopus
  30. H. Sun, J.-M. Zheng, S. Chen, C.-H. Zeng, Z.-H. Liu, and L.-S. Li, “Enhanced expression of ANGPTL2 in the microvascular lesions of diabetic glomerulopathy,” Nephron—Experimental Nephrology, vol. 105, no. 4, pp. e117–e123, 2007. View at Publisher · View at Google Scholar · View at Scopus
  31. E. P. Brennan, M. J. Morine, D. W. Walsh et al., “Next-generation sequencing identifies TGF-beta1-associated gene expression profiles in renal epithelial cells reiterated in human diabetic nephropathy,” Biochimica et Biophysica Acta—Molecular Basis of Disease, vol. 1822, no. 4, pp. 589–599, 2012. View at Publisher · View at Google Scholar · View at Scopus
  32. H. J. Baelde, M. Eikmans, P. P. Doran, D. W. P. Lappin, E. De Heer, and J. A. Bruijn, “Gene expression profiling in glomeruli from human kidneys with diabetic nephropathy,” American Journal of Kidney Diseases, vol. 43, no. 4, pp. 636–650, 2004. View at Publisher · View at Google Scholar · View at Scopus
  33. L. Fiorentino, M. Cavalera, S. Menini et al., “Loss of TIMP3 underlies diabetic nephropathy via FoxO1/STAT1 interplay,” EMBO Molecular Medicine, vol. 5, no. 3, pp. 441–455, 2013. View at Publisher · View at Google Scholar · View at Scopus
  34. X. Wang, J. Liu, J. Zhen et al., “Histone deacetylase 4 selectively contributes to podocyte injury in diabetic nephropathy,” Kidney International, vol. 86, no. 4, pp. 712–725, 2014. View at Publisher · View at Google Scholar · View at Scopus
  35. H. Schmid, A. Boucherot, Y. Yasuda et al., “Modular activation of nuclear factor-kappaB transcriptional programs in human diabetic nephropathy,” Diabetes, vol. 55, no. 11, pp. 2993–3003, 2006. View at Publisher · View at Google Scholar · View at Scopus
  36. P. Fiorina, A. Vergani, R. Bassi et al., “Role of podocyte B7-1 in diabetic nephropathy,” Journal of the American Society of Nephrology, vol. 25, no. 7, pp. 1415–1429, 2014. View at Google Scholar
  37. K. I. Woroniecka, A. S. D. Park, D. Mohtat, D. B. Thomas, J. M. Pullman, and K. Susztak, “Transcriptome analysis of human diabetic kidney disease,” Diabetes, vol. 60, no. 9, pp. 2354–2369, 2011. View at Publisher · View at Google Scholar · View at Scopus
  38. D. Verzola, L. Cappuccino, E. D'Amato et al., “Enhanced glomerular Toll-like receptor 4 expression and signaling in patients with type 2 diabetic nephropathy and microalbuminuria,” Kidney International, vol. 86, no. 6, pp. 1229–1243, 2014. View at Publisher · View at Google Scholar · View at Scopus
  39. M. T. Lindenmeyer, M. Kretzler, A. Boucherot et al., “Interstitial vascular rarefaction and reduced VEGF-A expression in human diabetic nephropathy,” Journal of the American Society of Nephrology, vol. 18, no. 6, pp. 1765–1776, 2007. View at Publisher · View at Google Scholar · View at Scopus
  40. J. Gerth, C. D. Cohen, U. Hopfer et al., “Collagen type VIII expression in human diabetic nephropathy,” European Journal of Clinical Investigation, vol. 37, no. 10, pp. 767–773, 2007. View at Publisher · View at Google Scholar · View at Scopus
  41. H. J. Baelde, M. Eikmans, D. W. P. Lappin et al., “Reduction of VEGF-A and CTGF expression in diabetic nephropathy is associated with podocyte loss,” Kidney International, vol. 71, no. 7, pp. 637–645, 2007. View at Publisher · View at Google Scholar · View at Scopus
  42. H. Kato, A. Gruenwald, J. H. Suh et al., “Wnt/β-catenin pathway in podocytes integrates cell adhesion, differentiation, and survival,” The Journal of Biological Chemistry, vol. 286, no. 29, pp. 26003–26015, 2011. View at Publisher · View at Google Scholar · View at Scopus
  43. R. Vasko, M. Koziolek, M. Ikehata et al., “Role of basic fibroblast growth factor (FGF-2) in diabetic nephropathy and mechanisms of its induction by hyperglycemia in human renal fibroblasts,” The American Journal of Physiology—Renal Physiology, vol. 296, no. 6, pp. F1452–F1463, 2009. View at Publisher · View at Google Scholar · View at Scopus
  44. Y. Yamaguchi, M. Iwano, D. Suzuki et al., “Epithelial-mesenchymal transition as a potential explanation for podocyte depletion in diabetic nephropathy,” American Journal of Kidney Diseases, vol. 54, no. 4, pp. 653–664, 2009. View at Publisher · View at Google Scholar · View at Scopus
  45. V. Dolan, M. Murphy, D. Sadlier et al., “Expression of gremlin, a bone morphogenetic protein antagonist, in human diabetic nephropathy,” American Journal of Kidney Diseases, vol. 45, no. 6, pp. 1034–1039, 2005. View at Publisher · View at Google Scholar · View at Scopus
  46. D. W. Walsh, S. A. Roxburgh, P. McGettigan et al., “Co-regulation of Gremlin and Notch signalling in diabetic nephropathy,” Biochimica et Biophysica Acta—Molecular Basis of Disease, vol. 1782, no. 1, pp. 10–21, 2008. View at Publisher · View at Google Scholar · View at Scopus
  47. M. T. Lindenmeyer, M. P. Rastaldi, M. Ikehata et al., “Proteinuria and hyperglycemia induce endoplasmic reticulum stress,” Journal of the American Society of Nephrology, vol. 19, no. 11, pp. 2225–2236, 2008. View at Publisher · View at Google Scholar · View at Scopus
  48. M. Murphy, N. G. Docherty, B. Griffin et al., “IHG-1 amplifies TGF-beta1 signaling and is increased in renal fibrosis,” Journal of the American Society of Nephrology, vol. 19, no. 9, pp. 1672–1680, 2008. View at Publisher · View at Google Scholar · View at Scopus
  49. M. B. Hookham, H. C. O'Donovan, R. H. Church et al., “Insulin receptor substrate-2 is expressed in kidney epithelium and up-regulated in diabetic nephropathy,” FEBS Journal, vol. 280, no. 14, pp. 3232–3243, 2013. View at Publisher · View at Google Scholar · View at Scopus
  50. C. C. Berthier, H. Zhang, M. Schin et al., “Enhanced expression of janus kinase-signal transducer and activator of transcription pathway members in human diabetic nephropathy,” Diabetes, vol. 58, no. 2, pp. 469–477, 2009. View at Publisher · View at Google Scholar · View at Scopus
  51. C. D. Cohen, M. T. Lindenmeyer, F. Eichinger et al., “Improved elucidation of biological processes linked to diabetic nephropathy by single probe-based microarray data analysis,” PLoS ONE, vol. 3, no. 8, Article ID e2937, 2008. View at Publisher · View at Google Scholar · View at Scopus
  52. T. Kuwabara, K. Mori, M. Kasahara et al., “Predictive significance of kidney myeloid-related protein 8 expression in patients with obesity- or type 2 diabetes-associated kidney diseases,” PLoS ONE, vol. 9, no. 2, Article ID e88942, 2014. View at Publisher · View at Google Scholar · View at Scopus
  53. C.-C. Szeto, K.-B. Lai, K.-M. Chow et al., “Messenger RNA expression of glomerular podocyte markers in the urinary sediment of acquired proteinuric diseases,” Clinica Chimica Acta, vol. 361, no. 1-2, pp. 182–190, 2005. View at Publisher · View at Google Scholar · View at Scopus
  54. M. Toyoda, D. Suzuki, T. Umezono et al., “Expression of human nephrin mRNA in diabetic nephropathy,” Nephrology Dialysis Transplantation, vol. 19, no. 2, pp. 380–385, 2004. View at Publisher · View at Google Scholar · View at Scopus
  55. T. Bondeva, C. Rüster, S. Franke et al., “Advanced glycation end-products suppress neuropilin-1 expression in podocytes,” Kidney International, vol. 75, no. 6, pp. 605–616, 2009. View at Publisher · View at Google Scholar · View at Scopus
  56. C. Lorz, A. Benito-Martín, A. Boucherot et al., “The death ligand TRAIL in diabetic nephropathy,” Journal of the American Society of Nephrology, vol. 19, no. 5, pp. 904–914, 2008. View at Publisher · View at Google Scholar
  57. R. G. Langham, D. J. Kelly, J. Maguire, J. P. Dowling, R. E. Gilbert, and N. M. Thomson, “Over-expression of platelet-derived growth factor in human diabetic nephropathy,” Nephrology Dialysis Transplantation, vol. 18, no. 7, pp. 1392–1396, 2003. View at Publisher · View at Google Scholar · View at Scopus
  58. I. Tossidou, B. Teng, J. Menne et al., “Podocytic PKC-alpha is regulated in murine and human diabetes and mediates nephrin endocytosis,” PLoS ONE, vol. 5, no. 4, Article ID e10185, 2010. View at Publisher · View at Google Scholar · View at Scopus
  59. R. G. Langham, D. J. Kelly, R. M. Gow et al., “Increased renal gene transcription of protein kinase C-beta in human diabetic nephropathy: relationship to long-term glycaemic control,” Diabetologia, vol. 51, no. 4, pp. 668–674, 2008. View at Publisher · View at Google Scholar · View at Scopus
  60. M. T. Lindenmeyer, F. Eichinger, K. Sen et al., “Systematic analysis of a novel human renal glomerulus-enriched gene expression dataset,” PLoS ONE, vol. 5, no. 7, Article ID e11545, 2010. View at Publisher · View at Google Scholar · View at Scopus
  61. T. H. Yoo, C. E. Pedigo, J. Guzman et al., “Sphingomyelinase-like phosphodiesterase 3b expression levels determine podocyte injury phenotypes in glomerular disease,” Journal of the American Society of Nephrology, vol. 26, no. 1, pp. 133–147, 2015. View at Google Scholar
  62. S. Zhang, Y. Zhang, X. Wei et al., “Expression and regulation of a novel identified TNFAIP8 family is associated with diabetic nephropathy,” Biochimica et Biophysica Acta, vol. 1802, no. 11, pp. 1078–1086, 2010. View at Publisher · View at Google Scholar · View at Scopus
  63. R. G. Langham, D. J. Kelly, R. M. Gow et al., “Increased expression of urotensin II and urotensin II receptor in human diabetic nephropathy,” American Journal of Kidney Diseases, vol. 44, no. 5, pp. 826–831, 2004. View at Publisher · View at Google Scholar · View at Scopus
  64. E. Bortoloso, D. Del Prete, M. Dalla Vestra et al., “Quantitave and qualitative changes in vascular endothelial growth factor gene expression in glomeruli of patients with type 2 diabetes,” European Journal of Endocrinology, vol. 150, no. 6, pp. 799–807, 2004. View at Publisher · View at Google Scholar · View at Scopus
  65. Y. Kanesaki, D. Suzuki, G. Uehara et al., “Vascular endothelial growth factor gene expression is correlated with glomerular neovascularization in human diabetic nephropathy,” American Journal of Kidney Diseases, vol. 45, no. 2, pp. 288–294, 2005. View at Publisher · View at Google Scholar · View at Scopus
  66. M. L. Alvarez, M. Khosroheidari, E. Eddy, and J. Kiefer, “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,” PLoS ONE, vol. 8, no. 10, Article ID e77468, 2013. View at Publisher · View at Google Scholar · View at Scopus
  67. Q. Wang, Y. Wang, A. W. Minto et al., “MicroRNA-377 is up-regulated and can lead to increased fibronectin production in diabetic nephropathy,” The FASEB Journal, vol. 22, no. 12, pp. 4126–4135, 2008. View at Publisher · View at Google Scholar · View at Scopus
  68. F. Barutta, M. Tricarico, A. Corbelli et al., “Urinary exosomal MicroRNAs in incipient diabetic nephropathy,” PLoS ONE, vol. 8, no. 11, Article ID e73798, 2013. View at Publisher · View at Google Scholar · View at Scopus
  69. Y. Huang, Y. Liu, L. Li et al., “Involvement of inflammation-related miR-155 and miR-146a in diabetic nephropathy: implications for glomerular endothelial injury,” BMC Nephrology, vol. 15, article 142, 2014. View at Publisher · View at Google Scholar · View at Scopus
  70. C.-C. Szeto, K. B. Ching-Ha, L. Ka-Bik et al., “Micro-RNA expression in the urinary sediment of patients with chronic kidney diseases,” Disease Markers, vol. 33, no. 3, pp. 137–144, 2012. View at Publisher · View at Google Scholar · View at Scopus
  71. C. Argyropoulos, K. Wang, S. McClarty et al., “Urinary microRNA profiling in the nephropathy of type 1 diabetes,” PLoS ONE, vol. 8, no. 1, Article ID e54662, 2013. View at Publisher · View at Google Scholar · View at Scopus
  72. A. Krupa, R. Jenkins, D. DongLuo, A. Lewis, A. Phillips, and D. Fraser, “Loss of microRNA-192 promotes fibrogenesis in diabetic nephropathy,” Journal of the American Society of Nephrology, vol. 21, no. 3, pp. 438–447, 2010. View at Publisher · View at Google Scholar · View at Scopus
  73. G. Wang, B. C.-H. Kwan, F. M.-M. Lai, K.-M. Chow, P. K.-T. Li, and C.-C. Szeto, “Urinary sediment miRNA levels in adult nephrotic syndrome,” Clinica Chimica Acta, vol. 418, pp. 5–11, 2013. View at Publisher · View at Google Scholar · View at Scopus
  74. L. Fiorentino, M. Cavalera, M. Mavilio et al., “Regulation of TIMP3 in diabetic nephropathy: a role for microRNAs,” Acta Diabetologica, vol. 50, no. 6, pp. 965–969, 2013. View at Publisher · View at Google Scholar · View at Scopus
  75. H. Peng, M. Zhong, W. Zhao et al., “Urinary miR-29 correlates with albuminuria and carotid intima-media thickness in type 2 diabetes patients,” PLoS ONE, vol. 8, no. 12, Article ID e82607, 2013. View at Publisher · View at Google Scholar · View at Scopus
  76. J. Zhou, R. Peng, T. Li et al., “A potentially functional polymorphism in the regulatory region of let-7a-2 is associated with an increased risk for diabetic nephropathy,” Gene, vol. 527, no. 2, pp. 456–461, 2013. View at Publisher · View at Google Scholar · View at Scopus
  77. J. Geisel, H. Schorr, G. H. Heine et al., “Decreased p66Shc promoter methylation in patients with end-stage renal disease,” Clinical Chemistry and Laboratory Medicine, vol. 45, no. 12, pp. 1764–1770, 2007. View at Publisher · View at Google Scholar · View at Scopus
  78. C. G. Bell, A. E. Teschendorff, V. K. Rakyan, A. P. Maxwell, S. Beck, and D. A. Savage, “Genome-wide DNA methylation analysis for diabetic nephropathy in type 1 diabetes mellitus,” BMC Medical Genomics, vol. 3, article 33, 2010. View at Publisher · View at Google Scholar · View at Scopus
  79. S. Nakatani, M. Wei, E. Ishimura et al., “Proteome analysis of laser microdissected glomeruli from formalin-fixed paraffin-embedded kidneys of autopsies of diabetic patients: nephronectin is associated with the development of diabetic glomerulosclerosis,” Nephrology, Dialysis, Transplantation, vol. 27, no. 5, pp. 1889–1897, 2012. View at Publisher · View at Google Scholar · View at Scopus
  80. A. A. Satoskar, J. P. Shapiro, C. N. Bott et al., “Characterization of glomerular diseases using proteomic analysis of laser capture microdissected glomeruli,” Modern Pathology, vol. 25, no. 5, pp. 709–721, 2012. View at Publisher · View at Google Scholar · View at Scopus
  81. S. S. Roscioni, D. De Zeeuw, M. E. Hellemons et al., “A urinary peptide biomarker set predicts worsening of albuminuria in type 2 diabetes mellitus,” Diabetologia, vol. 56, no. 2, pp. 259–267, 2013. View at Publisher · View at Google Scholar · View at Scopus
  82. D. Schlatzer, D. M. Maahs, M. R. Chance et al., “Novel urinary protein biomarkers predicting the development of microalbuminuria and renal function decline in type 1 diabetes,” Diabetes Care, vol. 35, no. 3, pp. 549–555, 2012. View at Publisher · View at Google Scholar · View at Scopus
  83. J. Jin, Y. H. Ku, Y. Kim et al., “Differential proteome profiling using iTRAQ in microalbuminuric and normoalbuminuric type 2 diabetic patients,” Experimental Diabetes Research, vol. 2012, Article ID 168602, 31 pages, 2012. View at Publisher · View at Google Scholar · View at Scopus
  84. H. Dihazi, G. A. Müller, S. Lindner et al., “Characterization of diabetic nephropathy by urinary proteomic analysis: identification of a processed ubiquitin form as a differentially excreted protein in diabetic nephropathy patients,” Clinical Chemistry, vol. 53, no. 9, pp. 1636–1645, 2007. View at Publisher · View at Google Scholar · View at Scopus
  85. M. Papale, S. Di Paolo, R. Magistroni et al., “Urine proteome analysis may allow noninvasive differential diagnosis of diabetic nephropathy,” Diabetes Care, vol. 33, no. 11, pp. 2409–2415, 2010. View at Publisher · View at Google Scholar · View at Scopus
  86. I. Zubiri, M. Posada-Ayala, A. Sanz-Maroto et al., “Diabetic nephropathy induces changes in the proteome of human urinary exosomes as revealed by label-free comparative analysis,” Journal of Proteomics, vol. 96, pp. 92–102, 2014. View at Publisher · View at Google Scholar · View at Scopus
  87. J.-M. Ahn, B.-G. Kim, M.-H. Yu, I.-K. Lee, and J.-Y. Cho, “Identification of diabetic nephropathy-selective proteins in human plasma by multi-lectin affinity chromatography and LC-MS/MS,” Proteomics—Clinical Applications, vol. 4, no. 6-7, pp. 644–653, 2010. View at Publisher · View at Google Scholar · View at Scopus
  88. M.-R. Kim, S.-A. Yu, M.-Y. Kim, K. M. Choi, and C.-W. Kim, “Analysis of glycated serum proteins in type 2 diabetes patients with nephropathy,” Biotechnology and Bioprocess Engineering, vol. 19, no. 1, pp. 83–92, 2014. View at Publisher · View at Google Scholar · View at Scopus
  89. E.-H. Cho, M.-R. Kim, H.-J. Kim et al., “The discovery of biomarkers for type 2 diabetic nephropathy by serum proteome analysis,” Proteomics—Clinical Applications, vol. 1, no. 4, pp. 352–361, 2007. View at Publisher · View at Google Scholar · View at Scopus
  90. K. Sharma, B. Karl, A. V. Mathew et al., “Metabolomics reveals signature of mitochondrial dysfunction in diabetic kidney disease,” Journal of the American Society of Nephrology, vol. 24, no. 11, pp. 1901–1912, 2013. View at Publisher · View at Google Scholar
  91. M. J. Pena, H. J. L. Heerspink, M. E. Hellemons et al., “Urine and plasma metabolites predict the development of diabetic nephropathy in individuals with type 2 diabetes mellitus,” Diabetic Medicine, vol. 31, no. 9, pp. 1138–1147, 2014. View at Publisher · View at Google Scholar · View at Scopus
  92. F. M. van der Kloet, F. W. A. Tempels, N. Ismail et al., “Discovery of early-stage biomarkers for diabetic kidney disease using ms-based metabolomics (FinnDiane study),” Metabolomics, vol. 8, no. 1, pp. 109–119, 2012. View at Publisher · View at Google Scholar · View at Scopus
  93. V. G. Marrachelli, D. Monleon, P. Rentero et al., “Genomic and metabolomic profile associated to microalbuminuria,” PLoS ONE, vol. 9, no. 6, Article ID e98227, 2014. View at Publisher · View at Google Scholar · View at Scopus
  94. A. Hirayama, E. Nakashima, M. Sugimoto et al., “Metabolic profiling reveals new serum biomarkers for differentiating diabetic nephropathy,” Analytical and Bioanalytical Chemistry, vol. 404, no. 10, pp. 3101–3109, 2012. View at Publisher · View at Google Scholar · View at Scopus
  95. J. Zhang, L. Yan, W. Chen et al., “Metabonomics research of diabetic nephropathy and type 2 diabetes mellitus based on UPLC-oaTOF-MS system,” Analytica Chimica Acta, vol. 650, no. 1, pp. 16–22, 2009. View at Publisher · View at Google Scholar · View at Scopus
  96. J.-F. Xia, Q.-L. Liang, X.-P. Liang et al., “Ultraviolet and tandem mass spectrometry for simultaneous quantification of 21 pivotal metabolites in plasma from patients with diabetic nephropathy,” Journal of Chromatography B: Analytical Technologies in the Biomedical and Life Sciences, vol. 877, no. 20-21, pp. 1930–1936, 2009. View at Publisher · View at Google Scholar · View at Scopus
  97. C. Zhu, Q.-L. Liang, P. Hu, Y.-M. Wang, and G.-A. Luo, “Phospholipidomic identification of potential plasma biomarkers associated with type 2 diabetes mellitus and diabetic nephropathy,” Talanta, vol. 85, no. 4, pp. 1711–1720, 2011. View at Publisher · View at Google Scholar · View at Scopus
  98. L.-D. Han, J.-F. Xia, Q.-L. Liang et al., “Plasma esterified and non-esterified fatty acids metabolic profiling using gas chromatography-mass spectrometry and its application in the study of diabetic mellitus and diabetic nephropathy,” Analytica Chimica Acta, vol. 689, no. 1, pp. 85–91, 2011. View at Publisher · View at Google Scholar · View at Scopus
  99. E. R. Seaquist, F. C. Goetz, S. Rich, and J. Barbosa, “Familial clustering of diabetic kidney disease,” The New England Journal of Medicine, vol. 320, no. 18, pp. 1161–1165, 1989. View at Publisher · View at Google Scholar · View at Scopus
  100. H. Kramer, W. Palmas, B. Kestenbaum et al., “Chronic kidney disease prevalence estimates among racial/ethnic groups: the multi-ethnic study of atherosclerosis,” Clinical Journal of the American Society of Nephrology, vol. 3, no. 5, pp. 1391–1397, 2008. View at Publisher · View at Google Scholar · View at Scopus
  101. A. R. Hipkiss, J. E. Preston, D. T. M. Himsworth et al., “Pluripotent protective effects of carnosine, a naturally occurring dipeptide,” Annals of the New York Academy of Sciences, vol. 854, no. 1, pp. 37–53, 1998. View at Publisher · View at Google Scholar · View at Scopus
  102. J. Makuc and D. Petrovic, “Diabetic nephropathy in type 2 diabetes: MPO T-764C genotype is associated with oxidative stress,” Central European Journal of Biology, vol. 7, no. 6, pp. 964–972, 2012. View at Publisher · View at Google Scholar · View at Scopus
  103. A. Shimazaki, Y. Tanaka, T. Shinosaki et al., “ELMO1 increases expression of extracellular matrix proteins and inhibits cell adhesion to ECMs,” Kidney International, vol. 70, no. 10, pp. 1769–1776, 2006. View at Publisher · View at Google Scholar · View at Scopus
  104. P. W. Mueller, J. J. Rogus, P. A. Cleary et al., “Genetics of Kidneys in Diabetes (GoKinD) study: a genetics collection available for identifying genetic susceptibility factors for diabetic nephropathy in type 1 diabetes,” Journal of the American Society of Nephrology, vol. 17, no. 7, pp. 1782–1790, 2006. View at Publisher · View at Google Scholar · View at Scopus
  105. M. G. Pezzolesi, G. D. Poznik, J. C. Mychaleckyj et al., “Genome-wide association scan for diabetic nephropathy susceptibility genes in type 1 diabetes,” Diabetes, vol. 58, no. 6, pp. 1403–1410, 2009. View at Publisher · View at Google Scholar · View at Scopus
  106. P. P. H. De Bruyn, S. Michelson, and R. P. Becker, “Endocytosis, transfer tubules, and lysosomal activity in myeloid sinusoidal endothelium,” Journal of Ultrastructure Research, vol. 53, no. 2, pp. 133–151, 1975. View at Publisher · View at Google Scholar · View at Scopus
  107. M. Ha and V. N. Kim, “Regulation of microRNA biogenesis,” Nature Reviews Molecular Cell Biology, vol. 15, no. 8, pp. 509–524, 2014. View at Publisher · View at Google Scholar · View at Scopus
  108. M. Inui, G. Martello, and S. Piccolo, “MicroRNA control of signal transduction,” Nature Reviews Molecular Cell Biology, vol. 11, no. 4, pp. 252–263, 2010. View at Publisher · View at Google Scholar · View at Scopus
  109. M. Kato, J. Zhang, M. Wang et al., “MicroRNA-192 in diabetic kidney glomeruli and its function in TGF-β-induced collagen expression via inhibition of E-box repressors,” Proceedings of the National Academy of Sciences of the United States of America, vol. 104, no. 9, pp. 3432–3437, 2007. View at Publisher · View at Google Scholar · View at Scopus
  110. A. Zarjou, S. Yang, E. Abraham, A. Agarwal, and G. Liu, “Identification of a microRNA signature in renal fibrosis: role of miR-21,” American Journal of Physiology—Renal Physiology, vol. 301, no. 4, pp. F793–F801, 2011. View at Publisher · View at Google Scholar · View at Scopus
  111. A. A. Eddy, “The TGF-beta route to renal fibrosis is not linear: the miR-21 viaduct,” Journal of the American Society of Nephrology, vol. 22, no. 9, pp. 1573–1575, 2011. View at Publisher · View at Google Scholar · View at Scopus
  112. M. L. Alvarez and J. K. DiStefano, “Functional characterization of the plasmacytoma variant translocation 1 gene (PVT1) in diabetic nephropathy,” PLoS ONE, vol. 6, no. 4, Article ID e18671, 2011. View at Publisher · View at Google Scholar · View at Scopus
  113. L. Pirola, A. Balcerczyk, J. Okabe, and A. El-Osta, “Epigenetic phenomena linked to diabetic complications,” Nature Reviews Endocrinology, vol. 6, no. 12, pp. 665–675, 2010. View at Publisher · View at Google Scholar · View at Scopus
  114. G. G. Camici, M. Schiavoni, P. Francia et al., “Genetic deletion of p66Shc adaptor protein prevents hyperglycemia-induced endothelial dysfunction and oxidative stress,” Proceedings of the National Academy of Sciences of the United States of America, vol. 104, no. 12, pp. 5217–5222, 2007. View at Publisher · View at Google Scholar · View at Scopus
  115. C. Sapienza, J. Lee, J. Powell et al., “DNA methylation profling identifes epigenetic differences between diabetes patients with ESRD and diabetes patients without nephropathy,” Epigenetics, vol. 6, no. 1, pp. 20–28, 2011. View at Publisher · View at Google Scholar · View at Scopus
  116. K. Hasegawa, S. Wakino, P. Simic et al., “Renal tubular Sirt1 attenuates diabetic albuminuria by epigenetically suppressing claudin-1 overexpression in podocytes,” Nature Medicine, vol. 19, no. 11, pp. 1496–1504, 2013. View at Publisher · View at Google Scholar · View at Scopus
  117. M. A. Reddy, P. Sumanth, L. Lanting et al., “Losartan reverses permissive epigenetic changes in renal glomeruli of diabetic db/db mice,” Kidney International, vol. 85, no. 2, pp. 362–373, 2014. View at Publisher · View at Google Scholar · View at Scopus
  118. M. Papale, S. Di Paolo, G. Vocino, M. T. Rocchetti, and L. Gesualdo, “Proteomics and diabetic nephropathy: what have we learned from a decade of clinical proteomics studies?” Journal of Nephrology, vol. 27, no. 3, pp. 221–228, 2014. View at Publisher · View at Google Scholar · View at Scopus
  119. B. Najafian, C. E. Alpers, and A. B. Fogo, “Pathology of human diabetic nephropathy,” Contributions to Nephrology, vol. 170, pp. 36–47, 2011. View at Publisher · View at Google Scholar · View at Scopus
  120. L. D. Ralton and G. I. Murray, “The use of formalin fixed wax embedded tissue for proteomic analysis,” Journal of Clinical Pathology, vol. 64, no. 4, pp. 297–302, 2011. View at Publisher · View at Google Scholar · View at Scopus
  121. M. R. Emmert-Buck, R. F. Bonner, P. D. Smith et al., “Laser capture microdissection,” Science, vol. 274, no. 5289, pp. 998–1001, 1996. View at Publisher · View at Google Scholar · View at Scopus
  122. A. Blutke, “Opening a treasure chest: glomerular proteome analyses of formalin-fixed paraffin-embedded kidney tissue in the investigation of diabetic nephropathy,” Nephrology, Dialysis, Transplantation, vol. 27, no. 5, pp. 1695–1698, 2012. View at Publisher · View at Google Scholar · View at Scopus
  123. J. M. Linton, G. R. Martin, and L. F. Reichardt, “The ECM protein nephronectin promotes kidney development via integrin α8β1-mediated stimulation of Gdnf expression,” Development, vol. 134, no. 13, pp. 2501–2509, 2007. View at Publisher · View at Google Scholar · View at Scopus
  124. K. Rossing, H. Mischak, M. Dakna et al., “Urinary proteomics in diabetes and CKD,” Journal of the American Society of Nephrology, vol. 19, no. 7, pp. 1283–1290, 2008. View at Publisher · View at Google Scholar · View at Scopus
  125. A. Alkhalaff, P. Zürbig, S. J. L. Bakker et al., “Multicentric validation of proteomic biomarkers in urine specific for diabetic nephropathy,” PLoS ONE, vol. 5, no. 10, Article ID e13421, 2010. View at Publisher · View at Google Scholar · View at Scopus
  126. P. Zürbig, G. Jerums, P. Hovind et al., “Urinary proteomics for early diagnosis in diabetic nephropathy,” Diabetes, vol. 61, no. 12, pp. 3304–3313, 2012. View at Publisher · View at Google Scholar · View at Scopus
  127. D. M. Good, P. Zürbig, A. Argilés et al., “Naturally occurring human urinary peptides for use in diagnosis of chronic kidney disease,” Molecular & Cellular Proteomics, vol. 9, no. 11, pp. 2424–2437, 2010. View at Publisher · View at Google Scholar
  128. T. Pisitkun, R.-F. Shen, and M. A. Knepper, “Identification and proteomic profiling of exosomes in human urine,” Proceedings of the National Academy of Sciences of the United States of America, vol. 101, no. 36, pp. 13368–13373, 2004. View at Publisher · View at Google Scholar · View at Scopus
  129. P. A. Gonzales, T. Pisitkun, J. D. Hoffert et al., “Large-scale proteomics and phosphoproteomics of urinary exosomes,” Journal of the American Society of Nephrology, vol. 20, no. 2, pp. 363–379, 2009. View at Publisher · View at Google Scholar · View at Scopus
  130. A. Vivekanandan-Giri, J. L. Slocum, C. L. Buller et al., “Urine glycoprotein profile reveals novel markers for chronic kidney disease,” International Journal of Proteomics, vol. 2011, Article ID 214715, 18 pages, 2011. View at Publisher · View at Google Scholar
  131. X. Fang and W.-W. Zhang, “Affinity separation and enrichment methods in proteomic analysis,” Journal of Proteomics, vol. 71, no. 3, pp. 284–303, 2008. View at Publisher · View at Google Scholar · View at Scopus
  132. H.-J. Kim, E.-H. Cho, J.-H. Yoo et al., “Proteome analysis of serum from type 2 diabetics with nephropathy,” Journal of Proteome Research, vol. 6, no. 2, pp. 735–743, 2007. View at Publisher · View at Google Scholar · View at Scopus
  133. H. G. Hansen, J. Overgaard, M. Lajer et al., “Finding diabetic nephropathy biomarkers in the plasma peptidome by high-throughput magnetic bead processing and MALDI-TOF-MS analysis,” Proteomics—Clinical Applications, vol. 4, no. 8-9, pp. 697–705, 2010. View at Publisher · View at Google Scholar · View at Scopus
  134. T. D. Veenstra, “Metabolomics: the final frontier?” Genome Medicine, vol. 4, no. 4, article 40, 2012. View at Publisher · View at Google Scholar · View at Scopus
  135. J. R. Bain, R. D. Stevens, B. R. Wenner, O. Ilkayeva, D. M. Muoio, and C. B. Newgard, “Metabolomics applied to diabetes research: moving from information to knowledge,” Diabetes, vol. 58, no. 11, pp. 2429–2443, 2009. View at Publisher · View at Google Scholar · View at Scopus
  136. S. J. Mihalik, B. H. Goodpaster, D. E. Kelley et al., “Increased levels of plasma acylcarnitines in obesity and type 2 diabetes and identification of a marker of glucolipotoxicity,” Obesity, vol. 18, no. 9, pp. 1695–1700, 2010. View at Publisher · View at Google Scholar · View at Scopus
  137. D. E. Kelley, J. He, E. V. Menshikova, and V. B. Ritov, “Dysfunction of mitochondria in human skeletal muscle in type 2 diabetes,” Diabetes, vol. 51, no. 10, pp. 2944–2950, 2002. View at Publisher · View at Google Scholar · View at Scopus
  138. K. C. B. Tan, S. W. M. Shiu, and Y. Wong, “Plasma phospholipid transfer protein activity and small, dense LDL in type 2 diabetes mellitus,” European Journal of Clinical Investigation, vol. 33, no. 4, pp. 301–306, 2003. View at Publisher · View at Google Scholar · View at Scopus
  139. L.-Q. Pang, Q.-L. Liang, Y.-M. Wang, L. Ping, and G.-A. Luo, “Simultaneous determination and quantification of seven major phospholipid classes in human blood using normal-phase liquid chromatography coupled with electrospray mass spectrometry and the application in diabetes nephropathy,” Journal of Chromatography B: Analytical Technologies in the Biomedical and Life Sciences, vol. 869, no. 1-2, pp. 118–125, 2008. View at Publisher · View at Google Scholar · View at Scopus
  140. J. M. Weinberg, “Lipotoxicity,” Kidney International, vol. 70, no. 9, pp. 1560–1566, 2006. View at Publisher · View at Google Scholar · View at Scopus