Redox Signaling in Diabetic Nephropathy: Hypertrophy versus Death Choices in Mesangial Cells and Podocytes

Mediators of Inflammation

Volumn 2015, Issue , 2015, Pages

  Manda, Gina ^a   Checherita, Alexandru Ionel ^a,b   Comanescu, Maria Victoria ^a,b   Hinescu, Mihail Eugen ^a,b  

^a VICTOR BABES NATIONAL INSTITUTE OF PATHOLOGY   (Romania)

^b CAROL DAVILA UNIVERSITY OF MEDICINE AND PHARMACY   (Romania)

Author keywords

[No Author keywords available]

Indexed keywords

PROTEIN KINASE; REACTIVE OXYGEN METABOLITE; REDUCED NICOTINAMIDE ADENINE DINUCLEOTIDE PHOSPHATE OXIDASE; TRANSCRIPTION FACTOR FOXO; ANTIOXIDANT; BIOLOGICAL MARKER;

AUTOPHAGY; CELL CYCLE ARREST; CELL DEATH; CELL FATE; CELL FUNCTION; CELL SURVIVAL; DIABETIC NEPHROPATHY; EARLY DIAGNOSIS; EXTRACELLULAR MATRIX; G1 PHASE CELL CYCLE CHECKPOINT; HUMAN; HYPERGLYCEMIA; HYPERTROPHY; INNATE IMMUNITY; KIDNEY TUBULE BASEMENT MEMBRANE; MESANGIUM CELL; NONHUMAN; OXIDATIVE STRESS; PATHOPHYSIOLOGY; PERSONALIZED MEDICINE; PODOCYTE; PROGNOSIS; PROTEIN EXPRESSION; PROTEIN PHOSPHORYLATION; PROTEIN PROCESSING; PROTEIN PROTEIN INTERACTION; REVIEW; SIGNAL TRANSDUCTION; TISSUE DISTRIBUTION; ANIMAL; CELL LINEAGE; GENETIC EPIGENESIS; INFLAMMATION; KIDNEY; METABOLISM; OXIDATION REDUCTION REACTION; PATHOLOGY;

ANIMALS; ANTIOXIDANTS; BIOMARKERS; CELL LINEAGE; DIABETIC NEPHROPATHIES; EPIGENESIS, GENETIC; HUMANS; HYPERTROPHY; INFLAMMATION; KIDNEY; MESANGIAL CELLS; OXIDATION-REDUCTION; OXIDATIVE STRESS; PODOCYTES; REACTIVE OXYGEN SPECIES; SIGNAL TRANSDUCTION;

EID: 84944237899     PISSN: 09629351     EISSN: 14661861     Source Type: Journal    
DOI: 10.1155/2015/604208     Document Type: Review

References (127)

1. N. Abdullah, J. Attia, C. Oldmeadow, R. J. Scott, and E. G. Holliday, "The architecture of risk for type 2 diabetes: understanding asia in the context of global findings," International Journal of Endocrinology, vol. 2014, Article ID 593982, 21 pages, 2014
2. World Health Organization, "Diabetes facts," http://www. who . int/mediacentre/factsheets/fs312/en/index. html
3. M. J. Fowler, "Microvascular and macrovascular complications of diabetes," Clinical Diabetes, vol. 26, no. 2, pp. 77-82, 2008
4. F. A. Rebolledo, J. M. T. Soto, and J. E. de la Peña, "The pathogenesis of the diabetic foot ulcer: prevention and management," in Global Perspective on Diabetic Foot Ulcerations, T. Dinh, Ed., InTech, 2011
5. 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
6. T. Gohda, A. Mima, J.-Y. Moon, and K. Kanasaki, "Combat diabetic nephropathy: frompathogenesis to treatment," Journal of Diabetes Research, vol. 2014, Article ID 207140, 2 pages, 2014
7. S. Dronavalli, I. Duka, and G. L. Bakris, "The pathogenesis of diabetic nephropathy," Nature Reviews Endocrinology, vol. 4, no. 8, pp. 444-452, 2008
8. B. K. Tiwari, K. B. Pandey, A. B. Abidi, and S. I. Rizvi, "Markers of oxidative stress during diabetes mellitus," Journal of Biomarkers, vol. 2013,Article ID 378790, 8 pages, 2013
9. M. Kalousová, J. Skrha, and T. Zima, "Advanced glycation endproducts and advanced oxidation protein products in patients with diabetes mellitus," Physiological Research, vol. 51, no. 6, pp. 597-604, 2002
10. V. M. Monnier, "Intervention against the Maillard reaction in vivo," Archives of Biochemistry and Biophysics, vol. 419, no. 1, pp. 1-15, 2003
11. T. J. Lyons and A. Basu, "Biomarkers in diabetes: hemoglobin A1c, vascular and tissue markers," Translational Research, vol. 159, no. 4, pp. 303-312, 2012
12. V. M. Monnier, O. Bautista, D. Kenny et al., "Skin collagen glycation, glycoxidation, and crosslinking are lower in subjects with long-term intensive versus conventional therapy of type 1 diabetes: relevance of glycated collagen products versus HbA1c as markers of diabetic complications. DCCT Skin Collagen Ancillary Study Group. Diabetes Control and Complications Trial," Diabetes, vol. 48, no. 4, pp. 870-880, 1999
13. P. J. Beisswenger, S. K. Howell, G. B. Russell,M. E. Miller, S. S. Rich, and M. Mauer, "Early progression of diabetic nephropathy correlates with methylglyoxal-derived advanced glycation end products," Diabetes Care, vol. 36, no. 10, pp. 3234-3239, 2013
14. C. Wang, C. C. Li, W. Y. Gong, and T. Lou, "New urinary biomarkers for diabetic kidney disease," Biomarker Research, vol. 1, p. 9, 2013
15. G. Manda, M. T. Nechifor, and T.-M. Neagu, "Reactive oxygen species, cancer and anti-cancer therapies," Current Chemical Biology, vol. 3, no. 1, pp. 22-46, 2009
16. R. P. Brandes, N. Weissmann, and K. Schröder, "Nox family NADPH oxidases: molecular mechanisms of activation," Free Radical Biology and Medicine, vol. 76, pp. 208-226, 2014
17. M. Brownlee, "Biochemistry and molecular cell biology of diabetic complications," Nature, vol. 414, no. 6865, pp. 813-820, 2001
18. L. L. Dugan, Y.-H. You, S. S. Ali et al., "AMPK dysregulation promotes diabetes-related reduction of superoxide and mitochondrial function," The Journal of Clinical Investigation, vol. 123, no. 11, pp. 4888-4899, 2013
19. S. Austin and J. St-Pierre, "PGC1 and mitochondrial metabolism-emerging concepts and relevance in ageing and neurodegenerative disorders," Journal of Cell Science, vol. 125, no. 21, pp. 4963-4971, 2012
20. M. S. Patel and L. G. Korotchkina, "Regulation of the pyruvate dehydrogenase complex," Biochemical Society Transactions, vol. 34, no. 2, pp. 217-222, 2006
21. F. Khoshjou and F. Dadras, "Mitochondrion and its role in diabetic nephropathy," Iranian Journal of Kidney Diseases, vol. 8, pp. 355-358, 2014
22. S. Wu, F. Zhou,Z. Zhang, and D. Xing, "Mitochondrialoxidative stress causes mitochondrial fragmentation via differential modulation ofmitochondrial fission-fusion proteins," FEBS Journal, vol. 278, no. 6, pp. 941-954, 2011
23. T. Yu, B. S. Jhun, and Y. Yoon, "High-glucose stimulation increases reactive oxygen species production through the calcium and mitogen-activated protein kinase-mediated activation of mitochondrial fission," Antioxidants and Redox Signaling, vol. 14, no. 3, pp. 425-437, 2011
24. G. Ashrafi and T. L. Schwarz, "The pathways of mitophagy for quality control and clearance of mitochondria," Cell Death and Differentiation, vol. 20, no. 1, pp. 31-42, 2013
25. G. C. Higgins and M. T. Coughlan, "Mitochondrial dysfunction and mitophagy: the beginning and end to diabetic nephropathy" British Journal of Pharmacology, vol. 171, no. 8, pp. 1917-1942, 2014
26. K. Yamahara, M. Yasuda, S. Kume, D. Koya, H. Maegawa, and T. Uzu, "The role of autophagy in the pathogenesis of diabetic nephropathy," Journal of Diabetes Research, vol. 2013,Article ID 193757, 9 pages, 2013
27. D. A. Towler, "Mitochondrial ROS deficiency and diabetic complications: AMP[K]-lifying the adaptation to hyperglycemia," The Journal of Clinical Investigation, vol. 123, no. 11, pp. 4573-4576, 2013
28. K. Bedard and K.-H. Krause, "The NOX family of ROSgeneratingNADPHoxidases: physiology and pathophysiology," Physiological Reviews, vol. 87, no. 1, pp. 245-313, 2007
29. T. Finkel, "Signal transduction by reactive oxygen species," The Journal of Cell Biology, vol. 194, no. 1, pp. 7-15, 2011
30. M. Sedeek, G. Callera, A. Montezano et al., "Critical role of Nox4-based NADPH oxidase in glucose-induced oxidative stress in the kidney: implications in type 2 diabetic nephropathy," The American Journal of Physiology-Renal Physiology, vol. 299, no. 6, pp. F1348-F1358, 2010
31. K. Block, Y. Gorin, and H. E. Abboud, "Subcellular localization ofNox4 and regulation in diabetes," Proceedings of the National Academy of Sciences of the United States of America, vol. 106, no. 34, pp. 14385-14390, 2009
32. M. Sedeek, A. Gutsol, A. C. Montezano et al., "Renoprotective effects of a novel Nox1/4 inhibitor in a mouse model of type 2 diabetes," Clinical Science, vol. 124, no. 3, pp. 191-202, 2013
33. J. C. Jha, S. P. Gray, D. Barit et al., "Genetic targeting or pharmacologic inhibition of NADPH oxidase Nox4 provides renoprotection in long-term diabetic nephropathy," Journal of the American Society of Nephrology, vol. 25, no. 6, pp. 1237-1254, 2014
34. B. Lassègue, A. San Martín, and K. K. Griendling, "Biochemistry, physiology, and pathophysiology of NADPH oxidases in the cardiovascular system," Circulation Research, vol. 110, no. 10, pp. 1364-1390, 2012
35. A. Babelova,D. Avaniadi,O. Jung et al., "Role ofNox4 inmurine models of kidney disease," Free Radical Biology and Medicine, vol. 53, no. 4, pp. 842-853, 2012
36. S. N. Khodo, E. Dizin, G. Sossauer et al., "NADPH-oxidase 4 protects against kidney fibrosis during chronic renal injury," Journal of the American Society of Nephrology, vol. 23, no. 12, pp. 1967-1976, 2012
37. Y. Gorin and K. Block, "Nox4 and diabetic nephropathy: with a friend like this, who needs enemies" Free Radical Biology and Medicine, vol. 61, pp. 130-142, 2013
38. H. H. H. W. Schmidt, K. Wingler, C. Kleinschnitz, and G. Dusting, "NOX4 is a Janus-faced reactive oxygen species generating NADPH oxidase," Circulation Research, vol. 111, pp. e15-e17, 2012
39. A. T. Dinkova-Kostova, W. D. Holtzclaw, R. N. Cole et al., "Direct evidence that sulfhydryl groups of Keap1 are the sensors regulating induction of phase 2 enzymes that protect against carcinogens and oxidants," Proceedings of the National Academy of Sciences of the United States of America, vol. 99, no. 18, pp. 11908-11913, 2002
40. V. Sharma and P. L. Sharma, "Role of different molecular pathways in the development of diabetes-induced nephropathy," Journal of Diabetes & Metabolism, supplement 9, article 004, 2013
41. Y. Hashimoto, S.-I. Yamagishi, H. Mizukami et al., "Polyol pathway and diabetic nephropathy revisited: early tubular cell changes and glomerulopathy in diabetic mice overexpressing human aldose reductase," Journal of Diabetes Investigation, vol. 2, no. 2, pp. 111-122, 2011
42. L. Zhang, B. Chen, and L. Tang, "Metabolic memory: mechanisms and implications for diabetic retinopathy," Diabetes Research and Clinical Practice, vol. 96, no. 3, pp. 286-293, 2012
43. N. C. Chilelli, S. Burlina, and A. Lapolla, "AGEs, rather than hyperglycemia, are responsible formicrovascular complications in diabetes: a 'glycoxidation-centric' point of view," Nutrition, Metabolism & Cardiovascular Diseases, vol. 23, no. 10, pp. 913-919, 2013
44. E. J. Lee and J. H. Park, "Receptor for advanced glycation endproducts (RAGE), its ligands, and soluble rage: potential biomarkers for diagnosis and therapeutic targets for human renal diseases," Genomics & Informatics, vol. 11, no. 4, pp. 224-229, 2013
45. J. M. Bohlender, S. Franke, G. Stein, and G. Wolf, "Advanced glycation end products and the kidney," The American Journal of Physiology-Renal Physiology, vol. 289, no. 4, pp. F645-F659, 2005
46. T. Matsui, S. Yamagishi, S. Ueda et al., "Telmisartan, an angiotensin II type 1 receptor blocker, inhibits advanced glycation end-product (AGE)-induced monocyte chemoattractant protein-1 expression in mesangial cells through downregulation of receptor for AGEs via peroxisome proliferatoractivated receptor-, activation," Journal of International Medical Research, vol. 35, no. 4, pp. 482-489, 2007
47. M. T. Coughlan, D. R. Thorburn, S. A. Penfold et al., "Rageinduced cytosolic ROS promote mitochondrial superoxide generation in diabetes," Journal of the American Society of Nephrology, vol. 20, no. 4, pp. 742-752, 2009
48. H. Cheng and R. C. Harris, "Renal endothelial dysfunction in diabetic nephropathy," Cardiovascular & Hematological Disorders-Drug Targets, vol. 14, pp. 22-33, 2014
49. G. K. Kolluru, S. C. Bir, and C. G. Kevil, "Endothelial dysfunction and diabetes: effects on angiogenesis, vascular remodeling, and wound healing," International Journal of VascularMedicine, vol. 2012, Article ID918267, 30 pages, 2012
50. S. S. Badal and F. R. Danesh, "Strategies to reverse endothelial dysfunction in diabetic nephropathy," Kidney International, vol. 82, no. 11, pp. 1151-1154, 2012
51. T. J. Guzik, S. Mussa, D. Gastaldi et al., "Mechanisms of increased vascular superoxide production in human diabetes mellitus: role of NAD(P)H oxidase and endothelial nitric oxide synthase," Circulation, vol. 105, no. 14, pp. 1656-1662, 2002
52. P. Pacher, J. S. Beckman, and L. Liaudet, "Nitric oxide and peroxynitrite in health and disease," Physiological Reviews, vol. 87, no. 1, pp. 315-424, 2007
53. E. Galkina and K. Ley, "Leukocyte recruitment and vascular injury in diabetic nephropathy," Journal of the American Society of Nephrology, vol. 17, no. 2, pp. 368-377, 2006
54. A. K. H. Lim and G. H. Tesch, "Inflammation in diabetic nephropathy," Mediators of Inflammation, vol. 2012, Article ID 146154, 12 pages, 2012
55. S. Y. Kassim, X. Fu, W. C. Liles, S. D. Shapiro, W. C. Parks, and J. W. Heinecke, "NADPH oxidase restrains the matrix metalloproteinase activity ofmacrophages," Journal of Biological Chemistry, vol. 280, no. 34, pp. 30201-30205, 2005
56. G. H. Tesch, "MCP-1/CCL2: a new diagnostic marker and therapeutic target for progressive renal injury in diabetic nephropathy," The American Journal of Physiology-Renal Physiology, vol. 294, no. 4, pp. F697-F701, 2008
57. A. Mantovani, A. Sica, S. Sozzani, P. Allavena, A. Vecchi, and M. Locati, "The chemokine systemin diverse forms ofmacrophage activation and polarization," Trends in Immunology, vol. 25, no. 12, pp. 677-686, 2004
58. J. J. Oppenheim and D. Yang, "Alarmins: chemotactic activators of immune responses," Current Opinion in Immunology, vol. 17, no. 4, pp. 359-365, 2005
59. P. Zhu, L. Xie, S. H. Ging, Q. Gong, J. Yang, and L. Yang, "High mobility group box 1 and kidney diseases," International Journal of Molecular Medicine, vol. 31, no. 4, pp. 763-768, 2013
60. T. Bonaldi, F. Talamo, P. Scaffidi et al., "Monocytic cells hyperacetylate chromatin proteinHMGB1 to redirect it towards secretion," The EMBO Journal, vol. 22, no. 20, pp. 5551-5560, 2003
61. U. Andersson and K. J. Tracey, "HMGB1 is a therapeutic target for sterile inflammation and infection," Annual Review of Immunology, vol. 29, pp. 139-162, 2011
62. E. Venereau, M. Casalgrandi, M. Schiraldi et al., "Mutually exclusive redox forms of HMGB1 promote cell recruitment or proinflammatory cytokine release," Journal of Experimental Medicine, vol. 209, no. 9, pp. 1519-1528, 2012
63. J. Kim, E. Sohn, C.-S. Kim, K. Jo, and J. S. Kim, "The role of highmobility group box-1 protein in the development of diabetic nephropathy," The American Journal of Nephrology, vol. 33, no. 6, pp. 524-529, 2011
64. M. Lin,W. H. Yiu, H. J. Wu et al., "Toll-like receptor 4 promotes tubular inflammation in diabetic nephropathy," Journal of the American Society of Nephrology, vol. 23, no. 1, pp. 86-102, 2012
65. G. Müller, "Microvesicles/exosomes as potential novel biomarkers of metabolic diseases," Diabetes, Metabolic Syndrome and Obesity: Targets and Therapy, vol. 5, pp. 247-282, 2012
66. E. Yoshihara, S. Masaki, Y. Matsuo, Z. Chen, H. Tian, and J. Yodoi, "Thioredoxin/txnip: redoxisome, as a redox switch for the pathogenesis of diseases," Frontiers in Immunology, vol. 4, article 514, 2014
67. Y. Hamada and M. Fukagawa, "A possible role of thioredoxin interacting protein in the pathogenesis of streptozotocininduced diabetic nephropathy," Kobe Journal of Medical Sciences, vol. 53, no. 2, pp. 53-61, 2007
68. I. Afanas'ev, "Signaling of reactive oxygen and nitrogen species in diabetes mellitus," OxidativeMedicine and Cellular Longevity, vol. 3, no. 6, pp. 361-373, 2010
69. S. S. Myatt and E. W.-F. Lam, "The emerging roles of forkhead box (Fox) proteins in cancer," Nature Reviews Cancer, vol. 7, no. 11, pp. 847-859, 2007
70. M. A. G. Essers, S. Weijzen, A. M. M. de Vries-Smits et al., "FOXO transcription factor activation by oxidative stress mediated by the small GTPase Ral and JNK," The EMBO Journal, vol. 23, no. 24, pp. 4802-4812, 2004
71. B. Ponugoti, G. Dong, and D. T. Graves, "Role of forkhead transcription factors in diabetes-induced oxidative stress," Experimental Diabetes Research, vol. 2012, Article ID 939751, 7 pages, 2012
72. P. Storz, "Forkhead homeobox type O transcription factors in the responses to oxidative stress," Antioxidants and Redox Signaling, vol. 14, no. 4, pp. 593-605, 2011
73. Z. Cheng, S. Guo, K. Copps et al., "Foxo1 integrates insulin signaling with mitochondrial function in the liver," Nature Medicine, vol. 15, no. 11, pp. 1307-1311, 2009
74. M. Alikhani, Z. Alikhani, and D. T. Graves, "FOXO1 functions as a master switch that regulates gene expression necessary for tumor necrosis factor-inducedfibroblast apoptosis,"TheJournal of Biological Chemistry, vol. 280, no. 13, pp. 12096-12102, 2005
75. E. N. Paniago and C. K. B. Ferrari, "Revisiting the pathology of thenuclear factorkappa beta," International Journal of Biological Chemistry, vol. 5, no. 5, pp. 291-299, 2011
76. M. Alikhani, S. Roy, and D. T. Graves, "FOXO1 plays anessential role in apoptosis of retinal pericytes," Molecular Vision, vol. 16, pp. 408-415, 2010
77. Y. Wang, Y. Zhou, and D. T. Graves, "FOXO transcription factors: their clinical significance and regulation," BioMed Research International, vol. 2014, Article ID 925350, 13 pages, 2014
78. H. Schmid, A. Boucherot, Y. Yasuda et al., "Modular activation of nuclear factor-B transcriptional programs in human diabetic nephropathy," Diabetes, vol. 55, no. 11, pp. 2993-3003, 2006
79. M. A. Reddy, J. Tak Park, and R. Natarajan, "Epigenetic modifications in the pathogenesis of diabetic nephropathy," Seminars in Nephrology, vol. 33, no. 4, pp. 341-353, 2013
80. E. Smith and A. Shilatifard, "The chromatin signaling pathway: diverse mechanisms of recruitment of histone-modifying enzymes and varied biological outcomes," Molecular Cell, vol. 40, no. 5, pp. 689-701, 2010
81. D. Siuda, U. Zechner, N. E. Hajj et al., "Transcriptional regulation of Nox4 by histone deacetylases in human endothelial cells," Basic Research in Cardiology, vol. 107, no. 5, article 283, 2012
82. G. Sun, M. A. Reddy, H. Yuan, L. Lanting, M. Kato, and R. Natarajan, "Epigenetic histone methylation modulates fibrotic gene expression," Journal of the American Society of Nephrology, vol. 21, no. 12, pp. 2069-2080, 2010
83. J. A. Baur, Z. Ungvari, R. K. Minor, D. G. Le Couteur, and R. de Cabo, "Are sirtuins viable targets for improving healthspan and lifespan" Nature Reviews Drug Discovery, vol. 11, pp. 443-461, 2012
84. R. Yacoub, K. Lee, and J. C. He, "The role of SIRT1 in diabetic kidney disease," Frontiers in Endocrinology, vol. 5, article 166, 2014
85. I. H. Lee, L. Cao, R. Mostoslavsky et al., "A role for the NADdependent deacetylase Sirt1 in the regulation of autophagy," Proceedings of the National Academy of Sciences of the United States of America, vol. 105, no. 9, pp. 3374-3379, 2008
86. K. A. Nath, "Therole of Sirt1 in renal rejuvenation and resistance to stress,"The Journal of Clinical Investigation, vol. 120, no. 4, pp. 1026-1028, 2010
87. C. Cantó, Z. Gerhart-Hines, J. N. Feige et al., "AMPK regulates energy expenditure by modulating NAD+ metabolism and SIRT1 activity," Nature, vol. 458, no. 7241, pp. 1056-1060, 2009
88. Y. Fu, Y. Zhang, Z. Wang et al., "Regulation of NADPH oxidase activity is associated with miRNA-25-mediated NOX4 expression in experimental diabetic nephropathy," American Journal of Nephrology, vol. 32, no. 6, pp. 581-589, 2010
89. S. Putta, L. Lanting, G. Sun, G. Lawson, M. Kato, and R. Natarajan, "Inhibiting microRNA-192 ameliorates renal fibrosis in diabetic nephropathy," Journal of the American Society of Nephrology, vol. 23, no. 3, pp. 458-469, 2012
90. J. J. Li, S. J. Kwak, D. S. Jung et al., "Podocyte biology in diabetic nephropathy," Kidney International, vol. 72, no. 106, pp. S36-S42, 2007
91. L. Mahimainathan, F. Das, B. Venkatesan, and G. G. Choudhury, "Mesangial cell hypertrophy by high glucose is mediated by downregulation of the tumor suppressor PTEN," Diabetes, vol. 55, no. 7, pp. 2115-2125, 2006
92. F. C. Brosius III, C. C. Khoury, C. L. Buller, and S. Chen, "Abnormalities in signaling pathways in diabetic nephropathy," Expert Review of Endocrinology and Metabolism, vol. 5, no. 1,pp. 51-64, 2010
93. L. Zhuo, B. Fu, X. Bai et al., "NAD blocks high glucose induced mesangial hypertrophy via activation of the sirtuins-AMPKmTOR pathway," Cellular Physiology and Biochemistry, vol. 27, no. 6, pp. 681-690, 2011
94. A. Y. M. Chan, V. W. Dolinsky,C.-L. M. Soltys et al., "Resveratrol inhibits cardiac hypertrophy via AMP-activated protein kinase and Akt," Journal of Biological Chemistry, vol. 283, no. 35, pp. 24194-24201, 2008
95. A. T. Petermann, J. Pippin, R. Durvasula et al., "Mechanical stretch induces podocyte hypertrophy in vitro," Kidney International, vol. 67, no. 1, pp. 157-166, 2005
96. T. Weide and T. B. Huber, "Implications of autophagy for glomerular aging and disease," Cell and Tissue Research, vol. 343, no. 3, pp. 467-473, 2011
97. T. Nakagawa, T. Kosugi, M. Haneda, C. J. Rivard, and D. A. Long, "Abnormal angiogenesis in diabetic nephropathy," Diabetes, vol. 58, no. 7, pp. 1471-1478, 2009
98. M. C. Iglesias-de la Cruz, F. N. Ziyadeh, M. Isono et al., "Effects of high glucose and TGF-1 on the expression of collagen IV and vascular endothelial growth factor in mouse podocytes," Kidney International, vol. 62, no. 3, pp. 901-913, 2002
99. M. B. Marrero, A. K. Banes-Berceli, D. M. Stern, and D. C. Eaton, "Role of the JAK/STAT signaling pathway in diabetic nephropathy," The American Journal of Physiology-Renal Physiology, vol. 290, no. 4, pp. F762-F768, 2006
100. R. J. Duhé, "Redox regulation of Janus kinase: the elephant in the room," JAKSTAT, vol. 2, no. 4, Article ID e28141, 2013
101. F. Matsui and K. K. Meldrum, "The role of the Janus kinase family/ signal transducer and activator of transcription signaling pathway in fibrotic renal disease," Journal of Surgical Research, vol. 178, no. 1, pp. 339-345, 2012
102. H. S. Lee, "Pathogenic role of TGF- in diabetic nephropathy," Journal of Diabetes & Metabolism, supplement 9, article 008, 2013
103. C. Dessapt, M. O. Baradez, A. Hayward et al., "Mechanical forces and TGF1 reduce podocyte adhesion through 31 integrin downregulation," Nephrology Dialysis Transplantation, vol. 24, no. 9, pp. 2645-2655, 2009
104. M. Schiffer, M. Bitzer, I. S. D. Roberts et al., "Apoptosis in podocytes induced by TGF- And Smad7," Journal of Clinical Investigation, vol. 108, no. 6, pp. 807-816, 2001
105. T. Niranjan, M. Murea, and K. Susztak, "The pathogenic role of notch activation in podocytes," Nephron Experimental Nephrology, vol. 111, no. 4, pp. e73-e79, 2009
106. A. L. Gartel and A. L. Tyner, "The role of the cyclin-dependent kinase inhibitor p21 in apoptosis," Molecular CancerTherapeutics, vol. 1, no. 8, pp. 639-649, 2002
107. P. Y. Chuang, Y. Dai, R. Liu et al., "Alteration of forkhead box O (foxo4) acetylationmediates apoptosis of podocytes in diabetes mellitus," PLoS ONE, vol. 6, no. 8,Article ID e23566, 2011
108. Q. Lu, Y. Zhai, Q. Cheng et al., "The Akt-FoxO3a-manganese superoxide dismutase pathway is involved in the regulation of oxidative stress in diabetic nephropathy," Experimental Physiology, vol. 98, no. 4, pp. 934-945, 2013
109. G. de Mattia, O. Laurenti, C. Bravi, A. Ghiselli, L. Iuliano, and F. Balsano, "Effect of aldose reductase inhibition on glutathione redox status in erythrocytes of diabetic patients," Metabolism, vol. 43, no. 8, pp. 965-968, 1994
110. V. Calabrese, C. Cornelius, V. Leso et al., "Oxidative stress, glutathione status, sirtuin and cellular stress response in type 2 diabetes," Biochimica et Biophysica Acta, vol. 1822, no. 5, pp. 729-736, 2012
111. L. Guarente and H. Franklin, "Epstein lecture: sirtuins, aging, and medicine," The New England Journal of Medicine, vol. 364, pp. 2235-2244, 2011
112. S. Akbar, S. Bellary, and H. R. Griffiths, "Dietary antioxidant interventions in type 2 diabetes patients: a meta-analysis," British Journal of Diabetes and Vascular Disease, vol. 11, no. 2, pp. 62-68, 2011
113. G. Bjelakovic, D. Nikolova, L. L. Gluud, R. G. Simonetti, and C. Gluud, "Mortality in randomized trials of antioxidant supplements for primary and secondary prevention: systematic review and meta-analysis," The Journal of the AmericanMedical Association, vol. 297, no. 8, pp. 842-857, 2007
114. H. K. Biesalski, T. Grune, J. Tinz, I. Zöllner, and J. B. Blumberg, "Reexamination of a meta-analysis of the effect of antioxidant supplementation onmortality and health in randomized trials," Nutrients, vol. 2, no. 9, pp. 929-949, 2010
115. S. C. Gupta, S. Patchva, and B. B. Aggarwal, "Therapeutic roles of curcumin: lessons learned fromclinical trials," AAPS Journal, vol. 15, no. 1, pp. 195-218, 2013
116. P. Khajehdehi, M. Pakfetrat, K. Javidnia et al., "Oral supplementation of turmeric attenuates proteinuria, transforming growth factor- And interleukin-8 levels in patients with overt type 2 diabetic nephropathy: a randomized, double-blind and placebo-controlled study," Scandinavian Journal of Urology and Nephrology, vol. 45, no. 5, pp. 365-370, 2011
117. J. W. Kaspar, S. K. Niture, and A. K. Jaiswal, "Nrf2:INrf2 (Keap1) signaling in oxidative stress," Free Radical Biology and Medicine, vol. 47, no. 9, pp. 1304-1309, 2009
118. J. B. de Haan, "Nrf2 activators as attractive therapeutics for diabetic nephropathy," Diabetes, vol. 60, no. 11, pp. 2683-2684, 2011
119. T. W. Kensler, N. Wakabayashi, and S. Biswal, "Cell survival responses to environmental stresses via the Keap1-Nrf2-ARE pathway," Annual Review of Pharmacology and Toxicology, vol. 47, pp. 89-116, 2007
120. A. Kobayashi, M.-I. Kang, Y. Watai et al., "Oxidative and electrophilic stresses activate Nrf2 through inhibition of ubiquitination activity ofKeap1,"Molecular and Cellular Biology, vol. 26, no. 1, pp. 221-229, 2006
121. N. Wakabayashi, S. L. Slocum, J. J. Skoko, S. Shin, and T. W. Kensler, "When NRF2 talks, who's listening" Antioxidants and Redox Signaling, vol. 13, no. 11, pp. 1649-1663, 2010
122. K. M. Holmstrom, L. Baird, Y. Zhang et al., "Nrf2 impacts cellular bioenergetics by controlling substrate availability for mitochondrial respiration," Biology Open, vol. 2, no. 8, pp. 761-770, 2013
123. C. Zoja, A. Benigni, and G. Remuzzi, "The Nrf2 pathway in the progression of renal disease," Nephrology Dialysis Transplantation, vol. 29, supplement 1, pp. i19-i24, 2014
124. H. Zheng, S. A. Whitman, W. Wu et al., "Therapeutic potential ofNrf2 activators in streptozotocin-induced diabetic nephropathy," Diabetes, vol. 60, no. 11, pp. 3055-3066, 2011
125. Y.-M. Go and D. P. Jones, "The redox proteome," Journal of Biological Chemistry, vol. 288, no. 37, pp. 26512-26520, 2013
126. A.-L. Barabási, N. Gulbahce, and J. Loscalzo, "Network medicine: a network-based approach to human disease," Nature Reviews Genetics, vol. 12, no. 1, pp. 56-68, 2011
127. L. Musante, D. E. Tataruch, and H. Holthofer, "Use and isolation of urinary exosomes as biomarkers for diabetic nephropathy," Frontiers in Endocrinology, vol. 5, article 149, 2014.