Diabetes and Kidney Disease: Role of Oxidative Stress

Antioxidants and Redox Signaling

Volumn 25, Issue 12, 2016, Pages 657-684

  Jha, Jay C ^a   Banal, Claudine ^a   Chow, Bryna S M ^a   Cooper, Mark E ^a,b   Jandeleit Dahm, Karin ^a,b  

^a BAKER IDI HEART AND DIABETES INSTITUTE   (Australia)

^b MONASH UNIVERSITY   (Australia)

Author keywords

albuminuria; diabetic nephropathy; NADPH oxidases; reactive oxygen species

Indexed keywords

ADVANCED OXIDATION PROTEIN PRODUCT; ANGIOTENSIN II; COLLAGEN TYPE 4; DIPEPTIDYL CARBOXYPEPTIDASE; FIBRONECTIN; GLUTATHIONE PEROXIDASE; HEXOSAMINE; HYDROGEN PEROXIDE; IMMUNOGLOBULIN ENHANCER BINDING PROTEIN; INTERLEUKIN 1; INTERLEUKIN 6; MITOGEN ACTIVATED PROTEIN KINASE; MONOCYTE CHEMOTACTIC PROTEIN 1; PLASMINOGEN ACTIVATOR INHIBITOR 1; PROTEIN KINASE B; PROTEIN KINASE C; PROTEIN KINASE C ALPHA; PROTEIN KINASE C BETA; PROTEIN SERINE THREONINE KINASE; REACTIVE OXYGEN METABOLITE; REDUCED NICOTINAMIDE ADENINE DINUCLEOTIDE PHOSPHATE OXIDASE; REDUCED NICOTINAMIDE ADENINE DINUCLEOTIDE PHOSPHATE OXIDASE 1; REDUCED NICOTINAMIDE ADENINE DINUCLEOTIDE PHOSPHATE OXIDASE 2; REDUCED NICOTINAMIDE ADENINE DINUCLEOTIDE PHOSPHATE OXIDASE 4; SODIUM GLUCOSE COTRANSPORTER 2; STRESS ACTIVATED PROTEIN KINASE; SUPEROXIDE DISMUTASE; TRANSFORMING GROWTH FACTOR BETA; TUMOR NECROSIS FACTOR; VASCULOTROPIN; ANTIOXIDANT;

ALBUMINURIA; APOPTOSIS; DIABETES MELLITUS; DIABETIC NEPHROPATHY; DNA DAMAGE; DOWN REGULATION; END STAGE RENAL DISEASE; ENDOTHELIAL DYSFUNCTION; FIBROSING ALVEOLITIS; GLOMERULOSCLEROSIS; GLOMERULUS FILTRATION RATE; HUMAN; HYPERTROPHY; KIDNEY DISEASE; LIPID PEROXIDATION; OXIDATIVE STRESS; PHASE 1 CLINICAL TRIAL (TOPIC); PHASE 2 CLINICAL TRIAL (TOPIC); PHASE 3 CLINICAL TRIAL (TOPIC); PRIORITY JOURNAL; PROTEIN EXPRESSION; PROTEIN MODIFICATION; RENIN ANGIOTENSIN ALDOSTERONE SYSTEM; REVIEW; VESTIBULAR DISORDER; ACUTE KIDNEY FAILURE; GENETICS; KIDNEY; METABOLISM; PATHOLOGY;

ACUTE KIDNEY INJURY; ANTIOXIDANTS; DIABETIC NEPHROPATHIES; HUMANS; KIDNEY; NADPH OXIDASE; OXIDATIVE STRESS; REACTIVE OXYGEN SPECIES;

EID: 84991706010     PISSN: 15230864     EISSN: 15577716     Source Type: Journal    
DOI: 10.1089/ars.2016.6664     Document Type: Review

References (295)

1. Ago T, Kitazono T, Ooboshi H, Iyama T, Han YH, Takada J, Wakisaka M, Ibayashi S, Utsumi H, and Iida M. Nox4 as the major catalytic component of an endothelial NAD(P)H oxidase. Circulation 109: 227-233, 2004.
2. Ago T, Kuribayashi F, Hiroaki H, Takeya R, Ito T, Kohda D, and Sumimoto H. Phosphorylation of p47phox directs phox homology domain from SH3 domain toward phosphoinositides, leading to phagocyte NADPH oxidase activation. Proc Natl Acad Sci U S A 100: 4474-4479, 2003.
3. Ago T, Kuroda J, Pain J, Fu C, Li H, and Sadoshima J. Upregulation of Nox4 by hypertrophic stimuli promotes apoptosis and mitochondrial dysfunction in cardiac myocytes. Circ Res 106: 1253-1264, 2010.
4. Akbar S, Bellary S, and Griffiths HR. Dietary antioxidant interventions in type 2 diabetes patients: a meta-analysis. Br J Diabetes Vasc Dis 11: 62-68, 2011.
5. Anvari E, Wikstrom P, Walum E, and Welsh N. The novel NADPH oxidase 4 inhibitor GLX351322 counteracts glucose intolerance in high-fat diet-treated C57BL/6 mice. Free Radic Res 49: 1308-1318, 2015.
6. Aoyama T, Paik YH, Watanabe S, Laleu B, Gaggini F, Fioraso-Cartier L, Molango S, Heitz F, Merlot C, Szyndralewiez C, Page P, and Brenner DA. Nicotinamide adenine dinucleotide phosphate oxidase in experimental liver fibrosis: GKT137831 as a novel potential therapeutic agent. Hepatology 56: 2316-2327, 2012.
7. Asaba K, Tojo A, Onozato ML, Goto A, Quinn MT, Fujita T, and Wilcox CS. Effects of NADPH oxidase inhibitor in diabetic nephropathy. Kidney Int 67: 1890-1898, 2005.
8. Attisano L and Wrana JL. Signal transduction by the TGFb superfamily. Science 296: 1646-1647, 2002.
9. Babelova A, Avaniadi D, Jung O, Fork C, Beckmann J, Kosowski J, Weissmann N, Anilkumar N, Shah AM, Schaefer L, Schroder K, and Brandes RP. Role of Nox4 in murine models of kidney disease. Free Radic Biol Med 53: 842-853, 2012.
10. Babior BM. NADPH oxidase: an update. Blood 93: 1464-1476, 1999.
11. BabiorBM, Kipnes RS, and Curnutte JT. Biological defense mechanisms. The production by leukocytes of superoxide, a potential bactericidal agent. J Clin Invest 52: 741-744, 1973.
12. Banfi B, Malgrange B, Knisz J, Steger K, Dubois-Dauphin M, and Krause KH. NOX3, a superoxide-generating NADPH oxidase of the inner ear. J Biol Chem279: 46065-46072, 2004.
13. Banfi B, Maturana A, Jaconi S, Arnaudeau S, Laforge T, Sinha B, Ligeti E, Demaurex N, and Krause KH. A mammalian H+ channel generated through alternative splicing of the NADPH oxidase homolog NOH-1. Science 287: 138-142, 2000.
14. Banfi B, Tirone F, Durussel I, Knisz J, Moskwa P, Molnar GZ, Krause KH, and Cox JA. Mechanism of Ca2+ activation of the NADPH oxidase 5 (NOX5). J Biol Chem 279: 18583-18591, 2004.
15. Baricos WH, Cortez SL, Deboisblanc M, and Xin S. Transforming growth factor-beta is a potent inhibitor of extracellular matrix degradation by cultured human mesangial cells. J Am Soc Nephrol 10: 790-795, 1999.
16. Barnes JL and Gorin Y. Myofibroblast differentiation during fibrosis: role of NAD(P)H oxidases. Kidney Int 79: 944-956, 2011.
17. Batandier C, Leverve X, and Fontaine E. Opening of the mitochondrial permeability transition pore induces reactive oxygen species production at the level of the respiratory chain complex I. J Biol Chem 279: 17197-17204, 2004.
18. Bedard K and Krause K-H. The NOX family of ROSgenerating NADPH oxidases: physiology and pathophysiology. Physiol Rev 87: 245-313, 2007.
19. BelAiba RS, Djordjevic T, Petry A, Diemer K, Bonello S, Banfi B, Hess J, Pogrebniak A, Bickel C, and Gorlach A. NOX5 variants are functionally active in endothelial cells. Free Radic Biol Med 42: 446-459, 2007.
20. Beyer RE. An analysis of the role of coenzyme Q in free radical generation and as an antioxidant. Biochem Cell Biol 70: 390-403, 1992.
21. Block K, Eid A, Griendling KK, Lee D-Y, Wittrant Y, and Gorin Y. Nox4 NAD(P)H oxidase mediates Src-dependent tyrosine phosphorylation of PDK-1 in response to angiotensin II: role in mesangial cell hypertrophy and fibronectin expression. J Biol Chem 283: 24061-24076, 2008.
22. Block K, Gorin Y, and Abboud HE. Subcellular localization of Nox4 and regulation in diabetes. Proc Natl Acad Sci U S A 106: 14385-14390, 2009.
23. Bokoch GM and Zhao T. Regulation of the phagocyte NADPH oxidase by Rac GTPase. Antioxid Redox Signal 8: 1533-1548, 2006.
24. Bondi CD, Manickam N, Lee DY, Block K, Gorin Y, Abboud HE, and Barnes JL. NAD(P)H oxidase mediates TGF-beta1-induced activation of kidney myofibroblasts. J Am Soc Nephrol 21: 93-102, 2010.
25. This reference has been deleted.
26. Bonventre JV and Weinberg JM. Recent advances in the pathophysiology of ischemic acute renal failure. J Am Soc Nephrol 14: 2199-2210, 2003.
27. Broekema M, Harmsen MC, van Luyn MJ, Koerts JA, Petersen AH, van Kooten TG, van Goor H, Navis G, and Popa ER. Bone marrow-derived myofibroblasts contribute to the renal interstitial myofibroblast population and produce procollagen I after ischemia/reperfusion in rats. J Am Soc Nephrol 18: 165-175, 2007.
28. Brosius FC. Susceptible mice: identifying a diabetic nephropathy disease locus using a murine model. Kidney Int 78: 431-432, 2010.
29. Brownlee M. Biochemistry and molecular cell biology of diabetic complications. Nature 414: 813-820, 2001.
30. Brownlee M. The pathobiology of diabetic complications: a unifying mechanism. Diabetes 54: 1615-1625, 2005.
31. This reference has been deleted.
32. Brunskill EW and Potter SS. Changes in the gene expression programs of renal mesangial cells during diabetic nephropathy. BMC Nephrol 13: 70, 2012.
33. Budanov AV. Stress-responsive sestrins link p53 with redox regulation and mammalian target of rapamycin signaling. Antioxid Redox Signal 15: 1679-1690, 2011.
34. Burns WC, Twigg SM, Forbes JM, Pete J, Tikellis C, Thallas-BonkeV, ThomasMC, CooperME, and Kantharidis P. Connective tissue growth factor plays an important role in advanced glycation end product-induced tubular epithelialto-mesenchymal transition: implications for diabetic renal disease. J Am Soc Nephrol 17: 2484-2494, 2006.
35. Chabrashvili T, Kitiyakara C, Blau J, Karber A, Aslam S, Welch WJ, and Wilcox CS. Effects of ANG II type 1 and 2 receptors on oxidative stress, renal NADPH oxidase, and SOD expression. Am J Physiol Regul Integr Comp Physiol 285: R117-R124, 2003.
36. Chabrashvili T, Tojo A, Onozato ML, Kitiyakara C, Quinn MT, Fujita T, Welch WJ, and Wilcox CS. Expression and cellular localization of classic NADPH oxidase subunits in the spontaneously hypertensive rat kidney. Hypertension 39: 269-274, 2002.
37. ChackoBalu K, ReilyC, Srivastava A, JohnsonMichelle S, Ye Y, Ulasova E, Agarwal A, Zinn Kurt R, Murphy Michael P, Kalyanaraman B, and Darley-Usmar V. Prevention of diabetic nephropathy in Ins2(+/-AkitaJ) mice by the mitochondriatargeted therapy MitoQ. Biochem J 432: 9-19, 2010.
38. Chalupsky K and Cai H. Endothelial dihydrofolate reductase: critical for nitric oxide bioavailability and role in angiotensin II uncoupling of endothelial nitric oxide synthase. Proc Natl Acad Sci U S A 102: 9056-9061, 2005.
39. Chang P-C, Chen T-H, Chang C-J, Hou C-C, Chan P, and Lee H-M. Advanced glycosylation end products induce inducible nitric oxide synthase (iNOS) expression via a p38 MAPKdependent pathway. Kidney Int 65: 1664-1675, 2004.
40. Chen J, Chen J-K, and Harris RC. Angiotensin II induces epithelial-to-mesenchymal transition in renal epithelial cells through reactive oxygen species/Src/caveolin-mediated activation of an epidermal growth factor receptor-extracellular signal-regulated kinase signaling pathway. Mol Cell Biol 32: 981-991, 2012.
41. This reference has been deleted.
42. Chen S, Jim B, and Ziyadeh FN. Diabetic nephropathy and transforming growth factor-beta: transforming our view of glomerulosclerosis and fibrosis build-up. Semin Nephrol 23: 532-543, 2003.
43. Cheng G, Cao Z, Xu X, van Meir EG, and Lambeth JD. Homologs of gp91phox: cloning and tissue expression of Nox3, Nox4, and Nox5. Gene 269: 131-140, 2001.
44. Cheng J and Grande JP. Transforming growth factor-beta signal transduction and progressive renal disease. Exp Biol Med (Maywood) 227: 943-956, 2002.
45. Chiarelli F, Cipollone F, Romano F, Tumini S, Costantini F, di Ricco L, Pomilio M, Pierdomenico SD, Marini M, Cuccurullo F, and Mezzetti A. Increased circulating nitric oxide in young patients with type 1 diabetes and persistent microalbuminuria: relation to glomerular hyperfiltration. Diabetes 49: 1258-1263, 2000.
46. Chow F, Ozols E, Nikolic-Paterson DJ, Atkins RC, and Tesch GH. Macrophages in mouse type 2 diabetic nephropathy: correlation with diabetic state and progressive renal injury. Kidney Int 65: 116-128, 2004.
47. Chow FY, Nikolic-Paterson DJ, Atkins RC, and Tesch GH. Macrophages in streptozotocin-induced diabetic nephropathy: potential role in renal fibrosis. Nephrol Dial Transplant 19: 2987-2996, 2004.
48. Clempus RE, Sorescu D, Dikalova AE, Pounkova L, Jo P, Sorescu GP, Schmidt HH, Lassegue B, and Griendling KK. Nox4 is required for maintenance of the differentiated vascular smooth muscle cell phenotype. Arterioscler Thromb Vasc Biol 27: 42-48, 2007.
49. Colas C and Ortiz de Montellano PR. Autocatalytic radical reactions in physiological prosthetic heme modification. Chem Rev 103: 2305-2332, 2003.
50. Cooper ME. Pathogenesis, prevention, and treatment of diabetic nephropathy. Lancet 352: 213-219, 1998.
51. Cooper ME, Mundel P, and Boner G. Role of nephrin in renal disease including diabetic nephropathy. Semin Nephrol 22: 393-398, 2002.
52. Cooper ME, Vranes D, Youssef S, Stacker SA, Cox AJ, Rizkalla B, Casley DJ, Bach LA, Kelly DJ, and Gilbert RE. Increased renal expression of vascular endothelial growth factor (VEGF) and its receptor VEGFR-2 in experimental diabetes. Diabetes 48: 2229-2239, 1999.
53. Coughlan MT, Thorburn DR, Penfold SA, Laskowski A, Harcourt BE, Sourris KC, Tan AL, Fukami K, Thallas-Bonke V, Nawroth PP, Brownlee M, Bierhaus A, Cooper ME, and Forbes JM. RAGE-induced cytosolic ROS promote mitochondrial superoxide generation in diabetes. J Am Soc Nephrol 20: 742-752, 2009.
54. This reference has been deleted.
55. Dalla Vestra M, Saller A, Mauer M, and Fioretto P. Role of mesangial expansion in the pathogenesis of diabetic nephropathy. J Nephrol 14 Suppl 4: S51-S57, 2001.
56. Das R, Xu S, Quan X, Nguyen TT, Kong ID, Chung CH, Lee EY, Cha SK, and Park KS. Upregulation of mitochondrial Nox4mediates TGF-beta-induced apoptosis in culturedmouse podocytes. AmJPhysiol Renal Physiol 306: F155-F167, 2014.
57. De Deken X, Wang D, Dumont JE, and Miot F. Characterization of ThOX proteins as components of the thyroid H(2)O(2)-generating system. Exp Cell Res 273: 187-196, 2002.
58. De Deken X, Wang D, Many MC, Costagliola S, Libert F, Vassart G, Dumont JE, and Miot F. Cloning of two human thyroid cDNAs encoding new members of the NADPH oxidase family. J Biol Chem 275: 23227-23233, 2000.
59. de Haan JB. Nrf2 activators as attractive therapeutics for diabetic nephropathy. Diabetes 60: 2683-2684, 2011.
60. De Vriese AS, Stoenoiu MS, Elger M, Devuyst O, Vanholder R, Kriz W, and Lameire NH. Diabetes-induced microvascular dysfunction in the hydronephrotic kidney: role of nitric oxide. Kidney Int 60: 202-210, 2001.
61. Decoursey TE and Ligeti E. Regulation and termination of NADPH oxidase activity. Cell Mol Life Sci 62: 2173-2193, 2005.
62. Deliyanti D and Wilkinson-Berka JL. Inhibition of NOX1/4 with GKT137831: a potential novel treatment to attenuate neuroglial cell inflammation in the retina. J Neuroinflammation 12: 136, 2015.
63. Dhaunsi GS, Kaur J, Alsaeid K, Turner RB, and Bitar MS. Very long chain fatty acids activate NADPH oxidase in human dermal fibroblasts. Cell Biochem Funct 23: 65-68, 2005.
64. Dikalov SI, Dikalova AE, Bikineyeva AT, Schmidt HH, Harrison DG, and Griendling KK. Distinct roles of Nox1 and Nox4 in basal and angiotensin II-stimulated superoxide and hydrogen peroxide production. Free Radic Biol Med 45: 1340-1351, 2008.
65. Ding G, Reddy K, Kapasi AA, Franki N, Gibbons N, Kasinath BS, and Singhal PC. Angiotensin II induces apoptosis in rat glomerular epithelial cells. Am J Physiol Renal Physiol 283: F173-F180, 2002.
66. Ding H, Aljofan M, and Triggle CR. Oxidative stress and increased eNOS and NADPH oxidase expression in mouse microvessel endothelial cells. J Cell Physiol 212: 682-689, 2007.
67. Ding Y, Chen ZJ, Liu S, Che D, Vetter M, and Chang CH. Inhibition of Nox-4 activity by plumbagin, a plant-derived bioactive naphthoquinone. J Pharm Pharmacol 57: 111-116, 2005.
68. Doublier S, Salvidio G, Lupia E, Ruotsalainen V, Verzola D, Deferrari G, and Camussi G. Nephrin expression is reduced in human diabetic nephropathy: evidence for a distinct role for glycated albumin and angiotensin II. Diabetes 52: 1023-1030, 2003.
69. Dugan LL, You Y-H, Ali SS, Diamond-Stanic M, Miyamoto S, DeCleves A-E, Andreyev A, Quach T, Ly S, Shekhtman G, Nguyen W, Chepetan A, Le TP, Wang L, Xu M, Paik KP, Fogo A, Viollet B, Murphy A, Brosius F, Naviaux RK, and Sharma K. AMPK dysregulation promotes diabetes-related reduction of superoxide and mitochondrial function. J Clin Invest 123: 4888-4899, 2013.
70. This reference has been deleted.
71. Dupuy C, Ohayon R, Valent A, Noel-Hudson MS, Deme D, andVirionA. Purification of a novel flavoprotein involved in the thyroid NADPH oxidase. Cloning of the porcine and human cdnas. J Biol Chem 274: 37265-37269, 1999.
72. Durvasula RV and Shankland SJ. Activation of a local renin angiotensin system in podocytes by glucose. Am J Physiol Renal Physiol 294: F830-F839, 2008.
73. Eid AA, Ford BM, Block K, Kasinath BS, Gorin Y, Ghosh-Choudhury G, Barnes JL, and Abboud HE. AMPactivated protein kinase (AMPK) negatively regulates Nox4-dependent activation of p53 and epithelial cell apoptosis in diabetes. J Biol Chem 285: 37503-37512, 2010.
74. Eid AA, Gorin Y, Fagg BM, Maalouf R, Barnes JL, Block K, and Abboud HE. Mechanisms of podocyte injury in diabetes: role of cytochrome P450 and NADPH oxidases. Diabetes 58: 1201-1211, 2009.
75. EidAA, LeeDY, RomanLJ, KhazimK, andGorin Y. Sestrin 2 and AMPK connect hyperglycemia to Nox4-dependent endothelial nitric oxide synthase uncoupling and matrix protein expression. Mol Cell Biol 33: 3439-3460, 2013.
76. El-Demerdash E, Awad AS, Taha RM, El-Hady AM, and Sayed-Ahmed MM. Probucol attenuates oxidative stress and energy decline in isoproterenol-induced heart failure in rat. Pharmacol Res 51: 311-318, 2005.
77. El Jamali A, Valente AJ, and Clark RA. Regulation of phagocyte NADPH oxidase by hydrogen peroxide through a Ca(2+)/c-Abl signaling pathway. Free Radic Biol Med 48: 798-810, 2010.
78. El Jamali A, Valente AJ, Lechleiter JD, Gamez MJ, Pearson DW, Nauseef WM, and Clark RA. Novel redoxdependent regulation of NOX5 by the tyrosine kinase c-Abl. Free Radic Biol Med 44: 868-881, 2008.
79. Elahi MM, Naseem KM, and Matata BM. Nitric oxide in blood. The nitrosative-oxidative disequilibrium hypothesis on the pathogenesis of cardiovascular disease. FEBS J 274: 906-923, 2007.
80. Etoh T, Inoguchi T, Kakimoto M, Sonoda N, Kobayashi K, Kuroda J, Sumimoto H, and Nawata H. Increased expression of NAD(P)H oxidase subunits, NOX4 and p22phox, in the kidney of streptozotocin-induced diabetic rats and its reversibity by interventive insulin treatment. Diabetologia 46: 1428-1437, 2003.
81. Feraille E, Dizin E, Roth I, Derouette JP, Szanto I, Martin PY, de Seigneux S, and Hasler U. NADPH oxidase 4 deficiency reduces aquaporin-2 mRNA expression in cultured renal collecting duct principal cells via increased PDE3 and PDE4 activity. PLoS One 9: e87239, 2014.
82. Ferreira SM, Lerner SF, Brunzini R, Evelson PA, and Llesuy SF. Oxidative stress markers in aqueous humor of glaucoma patients. Am J Ophthalmol 137: 62-69, 2004.
83. Forbes JM and Cooper ME. Mechanisms of diabetic complications. Physiol Rev 93: 137-188, 2013.
84. Forbes JM, Coughlan MT, and Cooper ME. Oxidative stress as a major culprit in kidney disease in diabetes. Diabetes 57: 1446-1454, 2008.
85. Ford BM, Eid AA, Gooz M, Barnes JL, Gorin YC, and Abboud HE. ADAM17 mediates Nox4 expression and NADPH oxidase activity in the kidney cortex of OVE26 mice. Am J Physiol Renal Physiol 305: F323-332, 2013.
86. Fu Y, Zhang Y, Wang Z, Wang L, Wei X, Zhang B, Wen Z, Fang H, Pang Q, and Yi F. Regulation of NADPH oxidase activity is associated with miRNA-25-mediated NOX4 expression in experimental diabetic nephropathy. Am J Nephrol 32: 581-589, 2010.
87. Fujii M, Inoguchi T, Maeda Y, Sasaki S, Sawada F, Saito R, Kobayashi K, Sumimoto H, and Takayanagi R. Pitavastatin ameliorates albuminuria and renal mesangial expansion by downregulating NOX4 in db/db mice. Kidney Int 72: 473-480, 2007.
88. Fulton DJ. Nox5 and the regulation of cellular function. Antioxid Redox Signal 11: 2443-2452, 2009.
89. Gaggini F, Laleu B, Orchard M, Fioraso-Cartier L, Cagnon L, Houngninou-Molango S, Gradia A, Duboux G, Merlot C, Heitz F, Szyndralewiez C, and Page P. Design, synthesis and biological activity of original pyrazolopyrido-diazepine,-pyrazine and-oxazine dione derivatives as novel dual Nox4/Nox1 inhibitors. Bioorg Med Chem 19: 6989-6999, 2011.
90. Gao L, Huang W, and Li J. NOX1 abet mesangial fibrogenesis via iNOS induction in diabetes. Mol Cell Biochem 382: 185-191, 2013.
91. Geiszt M, Kopp JB, Varnai P, and Leto TL. Identification of renox, an NAD(P)H oxidase in kidney. Proc Natl Acad Sci U S A 97: 8010-8014, 2000.
92. Gill PS and Wilcox CS. NADPH oxidases in the kidney. Antioxid Redox Signal 8: 1597-1607, 2006.
93. Giorgi C, Agnoletto C, Baldini C, Bononi A, Bonora M, Marchi S, Missiroli S, Patergnani S, Poletti F, Rimessi A, Zavan B, and Pinton P. Redox control of protein kinase C: cell-and disease-specific aspects. Antioxid Redox Signal 13: 1051-1085, 2010.
94. Gojo A, Utsunomiya K, Taniguchi K, Yokota T, Ishizawa S, Kanazawa Y, Kurata H, and Tajima N. The Rho-kinase inhibitor, fasudil, attenuates diabetic nephropathy in streptozotocin-induced diabetic rats. Eur J Pharmacol 568: 242-247, 2007.
95. Gorin Y and Block K. Nox4 and diabetic nephropathy: with a friend like this, who needs enemies? Free Radic Biol Med 61: 130-142, 2013.
96. Gorin Y, Block K, Hernandez J, Bhandari B, Wagner B, Barnes JL, and Abboud HE. Nox4 NAD(P)H oxidase mediates hypertrophy and fibronectin expression in the diabetic kidney. J Biol Chem 280: 39616-39626, 2005.
97. Gorin Y, Cavaglieri RC, Khazim K, Lee DY, Bruno F, Thakur S, Fanti P, Szyndralewiez C, Barnes JL, Block K, and Abboud HE. Targeting NADPH oxidase with a novel dual Nox1/Nox4 inhibitor attenuates renal pathology in type 1 diabetes. Am J Physiol Renal Physiol 308: F1276-1287, 2015.
98. This reference has been deleted.
99. Gorin Y, Ricono JM, Kim NH, Bhandari B, Choudhury GG, and Abboud HE. Nox4 mediates angiotensin IIinduced activation of Akt/protein kinase B in mesangial cells. Am J Physiol Renal Physiol 285: F219-F229, 2003.
100. Goyal P, Weissmann N, Rose F, Grimminger F, Schafers HJ, Seeger W, and Hanze J. Identification of novel Nox4 splice variants with impact on ROS levels in A549 cells. Biochem Biophys Res Commun 329: 32-39, 2005.
101. Graham S, Gorin Y, Abboud HE, Ding M, Lee DY, Shi H, Ding Y, and Ma R. Abundance of TRPC6 protein in glomerular mesangial cells is decreased by ROS and PKC in diabetes. Am J Physiol Cell Physiol 301: C304-C315, 2011.
102. Grasberger H and Refetoff S. Identification of the maturation factor for dual oxidase. Evolution of an eukaryotic operon equivalent. J Biol Chem 281: 18269-18272, 2006.
103. Gray SP, Di Marco E, Okabe J, Szyndralewiez C, Heitz F, Montezano AC, de Haan JB, Koulis C, El-Osta A, Andrews KL, Chin-Dusting JP, Touyz RM, Wingler K, Cooper ME, Schmidt HH, and Jandeleit-Dahm KA. NADPH oxidase 1 plays a key role in diabetes mellitus-accelerated atherosclerosis. Circulation 127: 1888-1902, 2013.
104. Greiber S, Munzel T, Kastner S, Muller B, Schollmeyer P, and Pavenstadt H. NAD(P)H oxidase activity in cultured human podocytes: effects of adenosine triphosphate. Kidney Int 53: 654-663, 1998.
105. Grobe AC, Wells SM, Benavidez E, Oishi P, Azakie A, Fineman JR, and Black SM. Increased oxidative stress in lambs with increased pulmonary blood flow and pulmonary hypertension: role of NADPH oxidase and endothelial NO synthase. Am J Physiol Lung Cell Mol Physiol 290: L1069-L1077, 2006.
106. Guijarro C and Egido J. Transcription factor-kappa B (NFkappa B) and renal disease. Kidney Int 59: 415-424, 2001.
107. GuzikTJ, ChenW, GongoraMC, GuzikB, Lob HE, Mangalat D, Hoch N, Dikalov S, Rudzinski P, Kapelak B, Sadowski J, and Harrison DG. Calcium dependent Nox5 NADPH oxidase contributes to vascular oxidative stress in human coronary artery disease. J Am Coll Cardiol 52: 1803-1809, 2008.
108. Harper RW, Xu C, Soucek K, Setiadi H, and Eiserich JP. A reappraisal of the genomic organization of human Nox1 and its splice variants. Arch Biochem Biophys 435: 323-330, 2005.
109. Harrison CB, Selemidis S, Guida E, King PT, Sobey CG, and Drummond GR. NOX2beta: a novel splice variant of NOX2 that regulates NADPH oxidase activity in macrophages. PLoS One 7: e48326, 2012.
110. He T, Guan X, Wang S, Xiao T, Yang K, Xu X, Wang J, and Zhao J. Resveratrol prevents high glucose-induced epithelial-mesenchymal transition in renal tubular epithelial cells by inhibiting NADPH oxidase/ROS/ERK pathway. Mol Cell Endocrinol 402: 13-20, 2015.
111. Hellemons ME, Kerschbaum J, Bakker SJ, Neuwirt H, Mayer B, Mayer G, de ZeeuwD, Lambers HeerspinkHJ, and Rudnicki M. Validity of biomarkers predicting onset or progression of nephropathy in patients with Type 2 diabetes: a systematic review. Diabet Med 29: 567-577, 2012.
112. Heumuller S, Wind S, Barbosa-Sicard E, Schmidt HH, Busse R, Schroder K, and Brandes RP. Apocynin is not an inhibitor of vascular NADPH oxidases but an antioxidant. Hypertension 51: 211-217, 2008.
113. Hilenski LL, Clempus RE, Quinn MT, Lambeth JD, and Griendling KK. Distinct subcellular localizations of Nox1 and Nox4 in vascular smooth muscle cells. Arterioscler Thromb Vasc Biol 24: 677-683, 2004.
114. Holterman CE, Thibodeau JF, Towaij C, Gutsol A, Montezano AC, Parks RJ, Cooper ME, Touyz RM, and Kennedy CR. Nephropathy and elevated BP in mice with podocyte-specific NADPH oxidase 5 expression. J Am Soc Nephrol 25: 784-797, 2014.
115. Hong NJ and Garvin JL. NADPH oxidase 4 mediates flowinduced superoxide production in thick ascending limbs. Am J Physiol Renal Physiol 303: F1151-F1156, 2012.
116. Hsieh TJ, Zhang SL, Filep JG, Tang SS, Ingelfinger JR, and Chan JS. High glucose stimulates angiotensinogen gene expression via reactive oxygen species generation in rat kidney proximal tubular cells. Endocrinology 143: 2975-2985, 2002.
117. Iglesias-de la Cruz MC, Ziyadeh FN, Isono M, Kouahou M, Han DC, Kalluri R, Mundel P, and Chen S. Effects of high glucose and TGF-beta1 on the expression of collagen IV and vascular endothelial growth factor in mouse podocytes. Kidney Int 62: 901-913, 2002.
118. Inoguchi T, Li P, Umeda F, Yu HY, Kakimoto M, Imamura M, Aoki T, Etoh T, Hashimoto T, NaruseM, SanoH, Utsumi H, and Nawata H. High glucose level and free fatty acid stimulate reactive oxygen species production through protein kinase C-dependent activation of NAD(P)H oxidase in cultured vascular cells. Diabetes 49: 1939-1945, 2000.
119. Iwano M and Neilson EG. Mechanisms of tubulointerstitial fibrosis. Curr Opin Nephrol Hypertens 13: 279-284, 2004.
120. Jaimes EA, Hua P, Tian R-X, and Raij L. Human glomerular endothelium: interplay among glucose, free fatty acids, angiotensin II, and oxidative stress. Am J Physiol Renal Physiol 298: F125-F132, 2010.
121. Jamaluddin M, Kim S, and Paik WK. Studies on the kinetic mechanism of S-adenosylmethionine: protein Omethyltransferase of calf thymus. Biochemistry 14: 694-698, 1975.
122. Jefferson JA, Shankland SJ, and Pichler RH. Proteinuria in diabetic kidney disease: a mechanistic viewpoint. Kidney Int 74: 22-36, 2008.
123. JerumsG, Panagiotopoulos S, andMacIsaacR. Podocytes and diabetic nephropathy. In: The Diabetic Kidney, edited by Cortes P and Mogensen C. Totowa, NJ: Humana Press, 2006, pp. 59-77.
124. Jha JC, Gray SP, Barit D, Okabe J, El-Osta A, Namikoshi T, Thallas-Bonke V, Wingler K, Szyndralewiez C, Heitz F, Touyz RM, Cooper ME, Schmidt HH, and Jandeleit-Dahm KA. Genetic targeting or pharmacologic inhibition of NADPH oxidase nox4 provides renoprotection in long-term diabetic nephropathy. J Am Soc Nephrol 25: 1237-1254, 2014.
125. Jha JC, Thallas-Bonke V, Banal C, Gray SP, Chow BS, Ramm G, Quaggin SE, Cooper ME, Schmidt HH, and Jandeleit-Dahm KA. Jandeleit-Dahm. Podocyte-specific Nox4 deletion affords renoprotection in a mouse model of diabetic nephropathy. Diabetologia 59: 379-389, 2016.
126. Jheng HF, Tsai PJ, Chuang YL, Shen YT, Tai TA, Chen WC, Chou CK, Ho LC, Tang MJ, Lai KT, Sung JM, and Tsai YS. Albumin stimulates renal tubular inflammation through an HSP70-TLR4 axis in mice with early diabetic nephropathy. Dis Model Mech 8: 1311-1321, 2015.
127. Jones SA, Donnell VB, Wood JD, Broughton JP, Hughes EJ, and Jones OT. Expression of phagocyte NADPH oxidase components in human endothelial cells. Am J Physiol Heart Circ Physiol 271: H1626-H1634, 1996.
128. Jones SA, Hancock JT, Jones OT, Neubauer A, and Topley N. The expression of NADPH oxidase components in human glomerular mesangial cells: detection of protein and mRNA for p47phox, p67phox, and p22phox. J Am Soc Nephrol 5: 1483-1491, 1995.
129. Kaneto H, Katakami N, Kawamori D, Miyatsuka T, Sakamoto K, Matsuoka TA, Matsuhisa M, and Yamasaki Y. Involvement of oxidative stress in the pathogenesis of diabetes. Antioxid Redox Signal 9: 355-366, 2007.
130. Kang SW, Adler SG, Lapage J, and Natarajan R. p38MAPK and MAPK kinase 3/6 mRNA and activities are increased in early diabetic glomeruli. Kidney Int 60: 543-552, 2001.
131. Kanwar YS, Wada J, Sun L, Xie P, Wallner EI, Chen S, Chugh S, and Danesh FR. Diabetic nephropathy: mechanisms of renal disease progression. Exp Biol Med (Maywood) 233: 4-11, 2008.
132. Karbach S, Jansen T, Horke S, Heeren T, Scholz A, Coldewey M, Karpi A, Hausding M, Kröller-Schön S, Oelze M, Münzel T, andDaiberA. Hyperglycemia and oxidative stress in cultured endothelial cells - a comparison of primary endothelial cells with an immortalized endothelial cell line. J Diabetes Complications 26: 155-162, 2012.
133. Kaspar JW, Niture SK, and Jaiswal AK. Nrf2:INrf2 (Keap1) Signaling in oxidative stress. Free Radic Biol Med 47: 1304-1309, 2009.
134. Kensler TW, Wakabayashi N, and Biswal S. Cell survival responses to environmental stresses via the Keap1-Nrf2-ARE pathway. Annu Rev Pharmacol Toxicol 47: 89-116, 2007.
135. Khazim K, Gorin Y, Cavaglieri RC, Abboud HE, and Fanti P. The antioxidant silybin prevents high glucoseinduced oxidative stress and podocyte injury in vitro and in vivo. Am J Physiol Renal Physiol 305: F691-700, 2013.
136. Kikuchi H, Hikage M, Miyashita H, and Fukumoto M. NADPH oxidase subunit, gp91(phox) homologue, preferentially expressed in human colon epithelial cells. Gene 254: 237-243, 2000.
137. Kim J, Shon E, Kim CS, and Kim JS. Renal podocyte injury in a rat model of type 2 diabetes is prevented by metformin. Exp Diabetes Res 2012: 210821, 2012.
138. Kim S-M, Kim Y-G, Jeong K-H, Lee S-H, Lee T-W, Ihm C-G, and Moon J-Y. Angiotensin II-induced mitochondrial Nox4 is a major endogenous source of oxidative stress in kidney tubular cells. PLoS One 7: e39739, 2012.
139. This reference has been deleted.
140. Kitada M, Koya D, Sugimoto T, Isono M, Araki S, Kashiwagi A, and Haneda M. Translocation of glomerular p47phox and p67phox by protein kinase C-beta activation is required for oxidative stress in diabetic nephropathy. Diabetes 52: 2603-2614, 2003.
141. Kitada M, Kume S, Imaizumi N, and Koya D. Resveratrol improves oxidative stress and protects against diabetic nephropathy through normalization of Mn-SOD dysfunction in AMPK/SIRT1-independent pathway. Diabetes 60: 634-643, 2011.
142. Klebanoff SJ. Oxygen metabolism and the toxic properties of phagocytes. Ann Intern Med 93: 480-489, 1980.
143. Klisic J, Nief V, Reyes L, and Ambuhl PM. Acute and chronic regulation of the renal Na/H+ exchanger NHE3 in rats with STZ-induced diabetes mellitus. Nephron Physiol 102: p27-p35, 2006.
144. Kolavennu V, Zeng L, Peng H, Wang Y, and Danesh FR. Targeting of RhoA/ROCK signaling ameliorates progression of diabetic nephropathy independent of glucose control. Diabetes 57: 714-723, 2008.
145. 2-.-mediated mitochondrial outgrowth. Am J Physiol Cell Physiol 288: C1440-C1450, 2005.
146. Kovac S, Angelova PR, Holmström KM, Zhang Y, Dinkova-Kostova AT, and Abramov AY. Nrf2 regulates ROS production by mitochondria and NADPH oxidase. Biochim Biophys Acta 1850: 794-801, 2015.
147. Koya D, Jirousek MR, Lin YW, Ishii H, Kuboki K, and King GL. Characterization of protein kinase C beta isoform activation on the gene expression of transforming growth factor-beta, extracellular matrix components, and prostanoids in the glomeruli of diabetic rats. J Clin Invest 100: 115-126, 1997.
148. Koziel R, Pircher H, Kratochwil M, Lener B, Hermann M, Dencher NA, and Jansen-Durr P. Mitochondrial respiratory chain complex I is inactivated by NADPH oxidase Nox4. Biochem J 452: 231-239, 2013.
149. Kuhad A and Chopra K. Attenuation of diabetic nephropathy by tocotrienol: involvement of NFkB signaling pathway. Life Sci 84: 296-301, 2009.
150. Kume S, Thomas MC, and Koya D. Nutrient Sensing, Autophagy, andDiabeticNephropathy. Diabetes 61: 23-29, 2012.
151. Laleu B, Gaggini F, Orchard M, Fioraso-Cartier L, Cagnon L, Houngninou-Molango S, Gradia A, Duboux G, Merlot C, Heitz F, Szyndralewiez C, and Page P. First in class, potent, and orally bioavailable NADPH oxidase isoform 4 (Nox4) inhibitors for the treatment of idiopathic pulmonary fibrosis. J Med Chem 53: 7715-7730, 2010.
152. Lassegue B and Clempus RE. Vascular NAD(P)H oxidases: specific features, expression, and regulation. Am J Physiol Regul Integr Comp Physiol 285: R277-R297, 2003.
153. Lassegue B, SanMartinA, andGriendlingKK. Biochemistry, physiology, and pathophysiology of NADPH oxidases in the cardiovascular system. Circ Res 110: 1364-1390, 2012.
154. Lee D-Y, Wauquier F, Eid AA, Roman LJ, Ghosh-Choudhury G, Khazim K, Block K, and Gorin Y. Nox4 NADPH oxidase mediates peroxynitrite-dependent uncoupling of endothelial nitric-oxide synthase and fibronectin expression in response to angiotensin II: role of mitochondrial reactive oxygen species. J Biol Chem 288: 28668-28686, 2013.
155. This reference has been deleted.
156. Lee HB, Yu M-R, Yang Y, Jiang Z, and Ha H. Reactive oxygen species-regulated signaling pathways in diabetic nephropathy. J Am Soc Nephrol 14: S241-S245, 2003.
157. This reference has been deleted.
158. Lee JH, Kim JH, Kim JS, Chang JW, Kim SB, Park JS, and Lee SK. AMP-activated protein kinase inhibits TGFbeta-, angiotensin II-, aldosterone-, high glucose-, and albumin-induced epithelial-mesenchymal transition. Am J Physiol Renal Physiol 304: F686-F697, 2013.
159. This reference has been deleted.
160. Li N, Yi FX, Spurrier JL, Bobrowitz CA, and Zou AP. Production of superoxide through NADH oxidase in thick ascending limb of Henle's loop in rat kidney. Am J Physiol Renal Physiol 282: F1111-F1119, 2002.
161. Liu BC, Song X, Lu XY, Li DT, Eaton DC, Shen BZ, Li XQ, and Ma HP. High glucose induces podocyte apoptosis by stimulating TRPC6 via elevation of reactive oxygen species. Biochim Biophys Acta 1833: 1434-1442, 2013.
162. Lorenz G, Darisipudi MN, and Anders H-J. Canonical and non-canonical effects of the NLRP3 inflammasome in kidney inflammation and fibrosis. Nephrol Dial Transplant 29: 41-48, 2014.
163. Lyle AN, Deshpande NN, Taniyama Y, Seidel-Rogol B, Pounkova L, Du P, Papaharalambus C, Lassegue B, and Griendling KK. Poldip2, a novel regulator of Nox4 and cytoskeletal integrity in vascular smooth muscle cells. Circ Res 105: 249-259, 2009.
164. Mahimainathan L, Das F, Venkatesan B, and Choudhury GG. Mesangial cell hypertrophy by high glucose is mediated by downregulation of the tumor suppressor PTEN. Diabetes 55: 2115-2125, 2006.
165. Manickam N, Patel M, Griendling KK, Gorin Y, and Barnes JL. RhoA/Rho kinase mediates TGF-beta1-induced kidney myofibroblast activation through Poldip2/Nox4-derived reactive oxygen species. Am J Physiol Renal Physiol 307: F159-F171, 2014.
166. Mariappan MM, Feliers D, Mummidi S, Choudhury GG, and Kasinath BS. High glucose, high insulin, and their combination rapidly induce laminin-beta1 synthesis by regulation of mRNA translation in renal epithelial cells. Diabetes 56: 476-485, 2007.
167. Martyn KD, Frederick LM, von Loehneysen K, Dinauer MC, and Knaus UG. Functional analysis of Nox4 reveals unique characteristics compared to other NADPH oxidases. Cell Signal 18: 69-82, 2006.
168. Mason RM and Wahab NA. Extracellular matrix metabolism in diabetic nephropathy. J Am Soc Nephrol 14: 1358-1373, 2003.
169. Massagué J and Gomis RR. The logic of TGFb signaling. FEBS Lett 580: 2811-2820, 2006.
170. Massey KJ, Hong NJ, and Garvin JL. Angiotensin II stimulates superoxide production in the thick ascending limb by activating NOX4. Am J Physiol Cell Physiol 303: C781-C789, 2012.
171. Matsuno K, Yamada H, Iwata K, Jin D, Katsuyama M, Matsuki M, Takai S, Yamanishi K, Miyazaki M, Matsubara H, and Yabe-Nishimura C. Nox1 is involved in angiotensin II-mediated hypertension: a study in Nox1-deficient mice. Circulation 112: 2677-2685, 2005.
172. Mauer SM, Steffes MW, Ellis EN, Sutherland DE, Brown DM, and Goetz FC. Structural-functional relationships in diabetic nephropathy. J Clin Invest 74: 1143-1155, 1984.
173. McGowan TA, Zhu Y, and Sharma K. Transforming growth factor-beta: a clinical target for the treatment of diabetic nephropathy. Curr Diab Rep 4: 447-454, 2004.
174. Mehrabian M, Sparkes RS, Mohandas T, Fogelman AM, and Lusis AJ. Localization of monocyte chemotactic protein-1 gene (SCYA2) to human chromosome 17q11. 2-q21. 1. Genomics 9: 200-203, 1991.
175. Michaud JL, Chaisson KM, Parks RJ, and Kennedy CR. FSGS-associated alpha-actinin-4 (K256E) impairs cytoskeletal dynamics in podocytes. Kidney Int 70: 1054-1061, 2006.
176. Mifsud SA, Allen TJ, Bertram JF, Hulthen UL, Kelly DJ, Cooper ME, Wilkinson-Berka JL, and Gilbert RE. Podocyte foot process broadening in experimental diabetic nephropathy: amelioration with renin-angiotensin blockade. Diabetologia 44: 878-882, 2001.
177. Modlinger P, Chabrashvili T, Gill PS, Mendonca M, Harrison DG, Griendling KK, Li M, Raggio J, Wellstein A, Chen Y, Welch WJ, and Wilcox CS. RNA silencing in vivo reveals role of p22phox in rat angiotensin slow pressor response. Hypertension 47: 238-244, 2006.
178. Molitch ME, DeFronzo RA, Franz MJ, Keane WF, Mogensen CE, Parving HH, and Steffes MW. Nephropathy in diabetes. Diabetes Care 27 Suppl 1: S79-S83, 2004.
179. Montero A, Munger KA, Khan RZ, Valdivielso JM, Morrow JD, Guasch A, Ziyadeh FN, and Badr KF. F(2)-isoprostanes mediate high glucose-induced TGF-beta synthesis and glomerular proteinuria in experimental type I diabetes. Kidney Int 58: 1963-1972, 2000.
180. Montezano AC, Burger D, Paravicini TM, Chignalia AZ, Yusuf H, AlmasriM, He Y, Callera GE, He G, Krause K-H, Lambeth D, Quinn MT, and Touyz RM. Nicotinamide adenine dinucleotide phosphate reduced oxidase 5 (Nox5) regulation by angiotensin II and endothelin-1 is mediated via calcium/calmodulin-dependent, Rac-1-independent pathways in human endothelial cells. Circ Res 106: 1363-1373, 2010.
181. This reference has been deleted.
182. Morgan MJ and Liu ZG. Crosstalk of reactive oxygen species and NF-kappaB signaling. Cell Res 21: 103-115, 2011.
183. Nagase M, Yoshida S, Shibata S, Nagase T, Gotoda T, Ando K, and Fujita T. Enhanced aldosterone signaling in the early nephropathy of rats with metabolic syndrome: possible contribution of fat-derived factors. J Am Soc Nephrol 17: 3438-3446, 2006.
184. Nakagawa T, Sato W, Sautin YY, Glushakova O, Croker B, Atkinson MA, Tisher CC, and Johnson RJ. Uncoupling of vascular endothelial growth factor with nitric oxide as a mechanismfor diabetic vasculopathy. J AmSocNephrol 17: 736-745, 2006.
185. Nakamura N, Matsui T, Ishibashi Y, and Yamagishi S. Insulin stimulates SGLT2-mediated tubular glucose absorption via oxidative stress generation. Diabetol Metab Syndr 7: 48, 2015.
186. Navarro JF, Milena FJ, Mora C, Leon C, and Garcia J. Renal pro-inflammatory cytokine gene expression in diabetic nephropathy: effect of angiotensin-converting enzyme inhibition and pentoxifylline administration. Am J Nephrol 26: 562-570, 2006.
187. New DD, Block K, Bhandhari B, Gorin Y, and Abboud HE. IGF-I increases the expression of fibronectin by Nox4-dependent Akt phosphorylation in renal tubular epithelial cells. Am J Physiol Cell Physiol 302: C122-C130, 2012.
188. Nishikawa T, Edelstein D, Du XL, Yamagishi S, Matsumura T, Kaneda Y, YorekMA, Beebe D, Oates PJ, Hammes H-P, Giardino I, and Brownlee M. Normalizing mitochondrial superoxide production blocks three pathways of hyperglycaemic damage. Nature 404: 787-790, 2000.
189. Nishiyama A, Yoshizumi M, Hitomi H, Kagami S, Kondo S, Miyatake A, Fukunaga M, Tamaki T, Kiyomoto H, Kohno M, Shokoji T, Kimura S, and Abe Y. The SOD mimetic tempol ameliorates glomerular injury and reduces mitogen-activated protein kinase activity in Dahl saltsensitive rats. J Am Soc Nephrol 15: 306-315, 2004.
190. Nistala R, Whaley-Connell A, and Sowers JR. Redox control of renal function and hypertension. Antioxid Redox Signal 10: 2047-2089, 2008.
191. Niu J and Kolattukudy PE. Role of MCP-1 in cardiovascular disease: molecular mechanisms and clinical implications. Clin Sci (Lond) 117: 95-109, 2009.
192. Nlandu Khodo S, Dizin E, Sossauer G, Szanto I, Martin PY, Feraille E, Krause KH, and de Seigneux S. NADPHoxidase 4 protects against kidney fibrosis during chronic renal injury. J Am Soc Nephrol 23: 1967-1976, 2012.
193. Oak JH and Cai H. Attenuation of angiotensin II signaling recouples eNOS and inhibits nonendothelial NOX activity in diabetic mice. Diabetes 56: 118-126, 2007.
194. Ohshiro Y, Ma RC, Yasuda Y, Hiraoka-Yamamoto J, Clermont AC, Isshiki K, Yagi K, Arikawa E, Kern TS, and King GL. Reduction of diabetes-induced oxidative stress, fibrotic cytokine expression, and renal dysfunction in protein kinase Cbeta-null mice. Diabetes 55: 3112-3120, 2006.
195. Olukman M, Orhan CE, Celenk FG, and Ulker S. Apocynin restores endothelial dysfunction in streptozotocin diabetic rats through regulation of nitric oxide synthase and NADPH oxidase expressions. J Diabetes Complications 24: 415-423, 2010.
196. Onozato ML, Tojo A, Goto A, Fujita T, and Wilcox CS. Oxidative stress and nitric oxide synthase in rat diabetic nephropathy: effects of ACEI and ARB. Kidney Int 61: 186-194, 2002.
197. Ozbek E. Induction of oxidative stress in kidney. Int J Nephrol 2012: 9, 2012.
198. Pacher P, Obrosova IG, Mabley JG, and Szabo C. Role of nitrosative stress and peroxynitrite in the pathogenesis of diabetic complications. Emerging new therapeutical strategies. Curr Med Chem 12: 267-275, 2005.
199. Paffenholz R, Bergstrom RA, Pasutto F, Wabnitz P, Munroe RJ, Jagla W, Heinzmann U, Marquardt A, Bareiss A, Laufs J, Russ A, Stumm G, Schimenti JC, and Bergstrom DE. Vestibular defects in head-tilt mice result from mutations in Nox3, encoding an NADPH oxidase. Genes Dev 18: 486-491, 2004.
200. Pagtalunan ME, Miller PL, Jumping-Eagle S, Nelson RG, Myers BD, Rennke HG, Coplon NS, Sun L, and Meyer TW. Podocyte loss and progressive glomerular injury in type II diabetes. J Clin Invest 99: 342-348, 1997.
201. Palicz A, Foubert TR, Jesaitis AJ, Marodi L, and McPhail LC. Phosphatidic acid and diacylglycerol directly activate NADPH oxidase by interacting with enzyme components. J Biol Chem 276: 3090-3097, 2001. 201a.
202. Pan Q, Yang X-H, Cheng Y-X. Angiotensin II stimulates MCP-1 production in rat glomerular endothelial cells via NAD(P)H oxidase-dependent nuclear factor-kappa B signaling. Braz J Med Biol Res 42: 531-536, 2009.
203. Pandey D, PatelA, Patel V, Chen F, Qian J, Wang Y, Barman SA, Venema RC, Stepp DW, Rudic RD, and Fulton DJ. Expression and functional significance ofNADPH oxidase 5 (Nox5) and its splice variants in human blood vessels. Am J Physiol Heart Circ Physiol 302: H1919-H1928, 2012.
204. Papadimitriou A, Peixoto EB, Silva KC, Lopes de Faria JM, and Lopes de Faria JB. Increase in AMPK brought about by cocoa is renoprotective in experimental diabetes mellitus by reducing NOX4/TGFbeta-1 signaling. J Nutr Biochem 25: 773-784, 2014.
205. Park HS, Chun JN, Jung HY, Choi C, and Bae YS. Role of NADPH oxidase 4 in lipopolysaccharide-induced proinflammatory responses by human aortic endothelial cells. Cardiovasc Res 72: 447-455, 2006.
206. Pecoits-Filho R, Lindholm B, Axelsson J, and Stenvinkel P. Update on interleukin-6 and its role in chronic renal failure. Nephrol Dial Transplant 18: 1042-1045, 2003.
207. Pedruzzi E, Guichard C, Ollivier V, Driss F, Fay M, Prunet C, Marie JC, Pouzet C, Samadi M, Elbim C, O'Dowd Y, Bens M, Vandewalle A, Gougerot-Pocidalo MA, Lizard G, and Ogier-Denis E. NAD(P)H oxidase Nox-4 mediates 7-ketocholesterol-induced endoplasmic reticulum stress and apoptosis in human aortic smooth muscle cells. Mol Cell Biol 24: 10703-10717, 2004.
208. Peng ZZ, Hu GY, Shen H, Wang L, Ning WB, Xie YY, Wang NS, Li BX, Tang YT, and Tao LJ. Fluorofenidone attenuates collagen I and transforming growth factor-beta1 expression through a nicotinamide adenine dinucleotide phosphate oxidase-dependent way in NRK-52E cells. Nephrology (Carlton) 14: 565-572, 2009.
209. Pergola PE, Krauth M, Huff JW, Ferguson DA, Ruiz S, Meyer CJ, and Warnock DG. Effect of bardoxolone methyl on kidney function in patients with T2D and Stage 3b-4 CKD. Am J Nephrol 33: 469-476, 2011.
210. Pergola PE, Raskin P, Toto RD, Meyer CJ, Huff JW, Grossman EB, KrauthM, Ruiz S, Audhya P, Christ-Schmidt H, Wittes J, Warnock DG, and Beam Study Investigators. Bardoxolonemethyl and kidney function inCKDwith type 2 diabetes. N Engl J Med 365: 327-336, 2011.
211. Persson P, Hansell P, and Palm F. NADPH oxidase inhibition reduces tubular sodium transport and improves kidney oxygenation in diabetes. Am J Physiol Regul Integr Comp Physiol 302: R1443-R1449, 2012.
212. Pieczenik SR and Neustadt J. Mitochondrial dysfunction and molecular pathways of disease. Exp Mol Pathol 83: 84-92, 2007.
213. Piwkowska A, Rogacka D, Audzeyenka I, Jankowski M, and Angielski S. High glucose concentration affects the oxidant-antioxidant balance in cultured mouse podocytes. J Cell Biochem 112: 1661-1672, 2011.
214. Pleskova M, Beck KF, Behrens MH, Huwiler A, Fichtlscherer B, Wingerter O, Brandes RP, Mulsch A, and Pfeilschifter J. Nitric oxide down-regulates the expression of the catalytic NADPH oxidase subunit Nox1 in rat renal mesangial cells. FASEB J 20: 139-141, 2006.
215. Qi W, Niu J, Qin Q, Qiao Z, and Gu Y. Glycated albumin triggers fibrosis and apoptosis via anNADPHoxidase/Nox4-MAPK pathway-dependent mechanism in renal proximal tubular cells. Mol Cell Endocrinol 405: 74-83, 2015.
216. Quack I, Woznowski M, Potthoff SA, Palmer R, Konigshausen E, Sivritas S, Schiffer M, Stegbauer J, Vonend O, Rump LC, and Sellin L. PKC alpha mediates beta-arrestin2-dependent nephrin endocytosis in hyperglycemia. J Biol Chem 286: 12959-12970, 2011.
217. Quaggin SE and Kreidberg JA. Development of the renal glomerulus: good neighbors and good fences. Development 135: 609-620, 2008.
218. Rhyu DY, Yang Y, Ha H, Lee GT, Song JS, Uh ST, and Lee HB. Role of reactive oxygen species in TGF-b1-induced mitogen-activated protein kinase activation and epithelial-mesenchymal transition in renal tubular epithelial cells. J Am Soc Nephrol 16: 667-675, 2005.
219. Riser BL, Denichilo M, Cortes P, Baker C, Grondin JM, Yee J, and Narins RG. Regulation of connective tissue growth factor activity in cultured rat mesangial cells and its expression in experimental diabetic glomerulosclerosis. J Am Soc Nephrol 11: 25-38, 2000.
220. Rosca MG, Mustata TG, Kinter MT, Ozdemir AM, Kern TS, Szweda LI, Brownlee M, Monnier VM, and Weiss MF. Glycation of mitochondrial proteins from diabetic rat kidney is associated with excess superoxide formation. Am J Physiol Renal Physiol 289: F420-F430, 2005.
221. Rosen P and Wiernsperger NF. Metformin delays the manifestation of diabetes and vascular dysfunction in Goto-Kakizaki rats by reduction of mitochondrial oxidative stress. Diabetes Metab Res Rev 22: 323-330, 2006.
222. Rossi F and Zatti M. Biochemical aspects of phagocytosis in polymorphonuclear leucocytes. NADH and NADPH oxidation by the granules of resting and phagocytizing cells. Experientia 20: 21-23, 1964.
223. Royer-Pokora B, Kunkel LM, Monaco AP, Goff SC, Newburger PE, Baehner RL, Cole FS, Curnutte JT, and Orkin SH. Cloning the gene for an inherited human disorder - chronic granulomatous disease - on the basis of its chromosomal location. Nature 322: 32-38, 1986.
224. Russo LM, del Re E, Brown D, and Lin HY. Evidence for a role of transforming growth factor (TGF)-beta1 in the induction of postglomerular albuminuria in diabetic nephropathy: amelioration by soluble TGF-beta type II receptor. Diabetes 56: 380-388, 2007.
225. Satchell SC and Tooke JE. What is the mechanism of microalbuminuria in diabetes: a role for the glomerular endothelium? Diabetologia 51: 714-725, 2008.
226. Schiffer M, Bitzer M, Roberts IS, Kopp JB, ten Dijke P, Mundel P, and Bottinger EP. Apoptosis in podocytes induced by TGF-beta and Smad7. J Clin Invest 108: 807-816, 2001.
227. Schluter T, Steinbach AC, Steffen A, Rettig R, and Grisk O. Apocynin-induced vasodilation involves Rho kinase inhibition but not NADPH oxidase inhibition. Cardiovasc Res 80: 271-279, 2008.
228. Schulz E, Jansen T, Wenzel P, Daiber A, and Munzel T. Nitric oxide, tetrahydrobiopterin, oxidative stress, and endothelial dysfunction in hypertension. Antioxid Redox Signal 10: 1115-1126, 2008.
229. Scotland RS, Chauhan S, Vallance PJ, and Ahluwalia A. An endothelium-derived hyperpolarizing factor-like factor moderates myogenic constriction of mesenteric resistance arteries in the absence of endothelial nitric oxide synthasederived nitric oxide. Hypertension 38: 833-839, 2001.
230. Sedeek M, Callera G, Montezano A, Gutsol A, Heitz F, Szyndralewiez C, Page P, Kennedy CR, Burns KD, Touyz RM, and Hebert RL. Critical role of Nox4-based NADPH oxidase in glucose-induced oxidative stress in the kidney: implications in type 2 diabetic nephropathy. Am J Physiol Renal Physiol 299: F1348-F1358, 2010.
231. Sedeek M, Gutsol A, Montezano AC, Burger D, Nguyen Dinh Cat A, Kennedy CR, Burns KD, Cooper ME, Jandeleit-Dahm K, Page P, Szyndralewiez C, Heitz F, Hebert RL, and Touyz RM. Renoprotective effects of a novel Nox1/4 inhibitor in a mouse model of Type 2 diabetes. Clin Sci (Lond) 124: 191-202, 2013.
232. Shah A, Xia L, Goldberg H, Lee KW, Quaggin SE, and Fantus IG. Thioredoxin-interacting protein mediates high glucose-induced reactive oxygen species generation by mitochondria and the NADPH oxidase, Nox4, in mesangial cells. J Biol Chem 288: 6835-6848, 2013.
233. Shahzad K, Bock F, Dong W, Wang H, Kopf S, Kohli S, Al-Dabet MdM, Ranjan S, Wolter J, Wacker C, Biemann R, Stoyanov S, Reymann K, Soderkvist P, Gros O, Schwenger V, Pahernik S, Nawroth PP, Grone H-J, Madhusudhan T, and Isermann B. Nlrp3-inflammasome activation in non-myeloid-derived cells aggravates diabetic nephropathy. Kidney Int 87: 74-84, 2015.
234. Sharma K and Ziyadeh FN. Renal hypertrophy is associated with upregulation of TGF-beta 1 gene expression in diabetic BB rat and NOD mouse. Am J Physiol 267: F1094-F1101, 1994.
235. Sheehan AL, Carrell S, Johnson B, Stanic B, Banfi B, and Miller FJ, Jr. Role for Nox1 NADPH oxidase in atherosclerosis. Atherosclerosis 216: 321-326, 2011.
236. Shi XY, Hou FF, Niu HX, Wang GB, Xie D, Guo ZJ, Zhou ZM, Yang F, Tian JW, and Zhang X. Advanced oxidation protein products promote inflammation in diabetic kidney through activation of renal nicotinamide adenine dinucleotide phosphate oxidase. Endocrinology 149: 1829-1839, 2008.
237. Shiose A, Kuroda J, Tsuruya K, Hirai M, Hirakata H, Naito S, Hattori M, Sakaki Y, and Sumimoto H. A novel superoxide-producing NAD(P)H oxidase in kidney. J Biol Chem 276: 1417-1423, 2001.
238. Soberman RJ. The expanding network of redox signaling: new observations, complexities, and perspectives. J Clin Invest 111: 571-574, 2003.
239. Soro-Paavonen A, Watson AM, Li J, Paavonen K, Koitka A, Calkin AC, Barit D, Coughlan MT, Drew BG, Lancaster GI, Thomas M, Forbes JM, Nawroth PP, Bierhaus A, Cooper ME, and Jandeleit-Dahm KA. Receptor for advanced glycation end products (RAGE) deficiency attenuates the development of atherosclerosis in diabetes. Diabetes 57: 2461-2469, 2008.
240. Stockand JD and Sansom SC. Glomerular mesangial cells: electrophysiology and regulation of contraction. Physiol Rev 78: 723-744, 1998.
241. Strutz F and Zeisberg M. Renal fibroblasts and myofibroblasts in chronic kidney disease. J Am Soc Nephrol 17: 2992-2998, 2006.
242. Suh YA, Arnold RS, Lassegue B, Shi J, Xu X, Sorescu D, Chung AB, Griendling KK, and Lambeth JD. Cell transformation by the superoxide-generating oxidase Mox1. Nature 401: 79-82, 1999.
243. Sumimoto H, Miyano K, and Takeya R. Molecular composition and regulation of the Nox family NAD(P)H oxidases. Biochem Biophys Res Commun 338: 677-686, 2005.
244. Sun P, Yue P, and Wang WH. Angiotensin II stimulates epithelial sodium channels in the cortical collecting duct of the rat kidney. Am J Physiol Renal Physiol 302: F679-F687, 2012.
245. Sung SH, Ziyadeh FN, Wang A, Pyagay PE, Kanwar YS, and Chen S. Blockade of vascular endothelial growth factor signaling ameliorates diabetic albuminuria in mice. J Am Soc Nephrol 17: 3093-3104, 2006.
246. Susztak K, Raff AC, Schiffer M, and Bottinger EP. Glucose-induced reactive oxygen species cause apoptosis of podocytes and podocyte depletion at the onset of diabetic nephropathy. Diabetes 55: 225-233, 2006.
247. This reference has been deleted.
248. Takac I, Schroder K, Zhang L, Lardy B, Anilkumar N, Lambeth JD, Shah AM, Morel F, and Brandes RP. The Eloop is involved in hydrogen peroxide formation by the NADPH oxidase Nox4. J Biol Chem 286: 13304-13313, 2011.
249. Tan ALY, Sourris KC, Harcourt BE, Thallas-Bonke V, Penfold S, Andrikopoulos S, Thomas MC, Brien RC, Bierhaus A, Cooper ME, Forbes JM, and Coughlan MT. Disparate effects on renal and oxidative parameters following RAGE deletion, AGE accumulation inhibition, or dietary AGE control in experimental diabetic nephropathy. Am J Physiol Renal Physiol 298: F763-F770, 2010.
250. TeahanC, Rowe P, Parker P, TottyN, and SegalAW. TheXlinked chronic granulomatous disease gene codes for the beta-chain of cytochrome b-245. Nature 327: 720-721, 1987.
251. Tesch GH. MCP-1/CCL2: a new diagnostic marker and therapeutic target for progressive renal injury in diabetic nephropathy. Am J Physiol Renal Physiol 294: F697-F701, 2008.
252. Thallas-Bonke V, Jha JC, Gray SP, Barit D, Haller H, Schmidt HH, Coughlan MT, Cooper ME, Forbes JM, and Jandeleit-Dahm KA. Nox-4 deletion reduces oxidative stress and injury by PKC-alpha-associated mechanisms in diabetic nephropathy. Physiol Rep 2: pii: e12192, 2014.
253. Thallas-Bonke V, Thorpe SR, Coughlan MT, Fukami K, Yap FY, Sourris KC, Penfold SA, Bach LA, Cooper ME, and Forbes JM. Inhibition of NADPH oxidase prevents advanced glycation end product-mediated damage in diabetic nephropathy through a protein kinase C-alphadependent pathway. Diabetes 57: 460-469, 2008.
254. Thannickal VJ and Fanburg BL. Reactive oxygen species in cell signaling. Am J Physiol Lung Cell Mol Physiol 279: L1005-L1028, 2000.
255. Tojo A, Asaba K, and Onozato ML. Suppressing renal NADPH oxidase to treat diabetic nephropathy. Expert Opin Ther Targets 11: 1011-1018, 2007.
256. Tojo A, Onozato ML, Kobayashi N, Goto A, Matsuoka H, and Fujita T. Antioxidative effect of p38 mitogenactivated protein kinase inhibitor in the kidney of hypertensive rat. J Hypertens 23: 165-174, 2005.
257. Toto RD, Tian M, Fakouhi K, Champion A, and Bacher P. Effects of calcium channel blockers on proteinuria in patients with diabetic nephropathy. J Clin Hypertens (Greenwich) 10: 761-769, 2008.
258. Tsilibary EC. Microvascular basement membranes in diabetes mellitus. J Pathol 200: 537-546, 2003.
259. Vallet P, Charnay Y, Steger K, Ogier-Denis E, Kovari E, Herrmann F, Michel JP, and Szanto I. Neuronal expression of the NADPH oxidase NOX4, and its regulation in mouse experimental brain ischemia. Neuroscience 132: 233-238, 2005.
260. Vallon V, Platt KA, Cunard R, Schroth J, Whaley J, Thomson SC, Koepsell H, and Rieg T. SGLT2 mediates glucose reabsorption in the early proximal tubule. J Am Soc Nephrol 22: 104-112, 2011.
261. Wada T, Sakai N, Matsushima K, and Kaneko S. Fibrocytes: a new insight into kidney fibrosis. Kidney Int 72: 269-273, 2007.
262. Wahab NA, Schaefer L, Weston BS, Yiannikouris O, Wright A, Babelova A, Schaefer R, and Mason RM. Glomerular expression of thrombospondin-1, transforming growth factor beta and connective tissue growth factor at different stages of diabetic nephropathy and their interdependent roles in mesangial response to diabetic stimuli. Diabetologia 48: 2650-2660, 2005.
263. Wang D, De Deken X, Milenkovic M, Song Y, Pirson I, Dumont JE, and Miot F. Identification of a novel partner of duox: EFP1, a thioredoxin-related protein. J Biol Chem 280: 3096-3103, 2005.
264. Wang H, Chen X, Su Y, Paueksakon P, Hu W, Zhang MZ, Harris RC, Blackwell TS, Zent R, and Pozzi A. p47(phox) contributes to albuminuria and kidney fibrosis in mice. Kidney Int 87: 948-962, 2015.
265. Wang HJ, Huang YL, Shih YY, Wu HY, Peng CT, and Lo WY. MicroRNA-146a decreases high glucose/thrombininduced endothelial inflammation by inhibiting NAPDH oxidase 4 expression. Mediators Inflamm 2014: 379537, 2014.
266. Wang S, Aurora AB, Johnson BA, Qi X, McAnally J, Hill JA, Richardson JA, Bassel-Duby R, and Olson EN. An endothelial-specific microRNA governs vascular integrity and angiogenesis. Dev Cell 15: 261-271, 2008.
267. Wei XF, Zhou QG, Hou FF, Liu BY, and Liang M. Advanced oxidation protein products induce mesangial cell perturbation through PKC-dependent activation of NADPH oxidase. Am J Physiol Renal Physiol 296: F427-F437, 2009.
268. Weston BS, Wahab NA, and Mason RM. CTGF mediates TGF-beta-induced fibronectin matrix deposition by upregulating active alpha5beta1 integrin in human mesangial cells. J Am Soc Nephrol 14: 601-610, 2003.
269. Whaley-Connell A, Habibi J, Nistala R, Cooper SA, Karuparthi PR, Hayden MR, Rehmer N, DeMarco VG, Andresen BT, Wei Y, Ferrario C, and Sowers JR. Attenuation of NADPH oxidase activation and glomerular filtration barrier remodeling with statin treatment. Hypertension 51: 474-480, 2008.
270. Wingler K, Wunsch S, Kreutz R, Rothermund L, Paul M, and Schmidt HH. Upregulation of the vascular NAD(P)Hoxidase isoforms Nox1 and Nox4 by the renin-angiotensin system in vitro and in vivo. Free Radic Biol Med 31: 1456-1464, 2001.
271. Winiarska K, Jarzyna R, Dzik JM, Jagielski AK, Grabowski M, Nowosielska A, Focht D, and Sierakowski B. ERK1/2 pathway is involved in renal gluconeogenesis inhibition under conditions of lowered NADPH oxidase activity. Free Radic Biol Med 81: 13-21, 2015.
272. Wolf G, Chen S, and Ziyadeh FN. From the periphery of the glomerular capillary wall toward the center of disease: podocyte injury comes of age in diabetic nephropathy. Diabetes 54: 1626-1634, 2005.
273. Wolf G, Mueller E, Stahl RA, and Ziyadeh FN. Angiotensin II-induced hypertrophy of cultured murine proximal tubular cells is mediated by endogenous transforming growth factor-beta. J Clin Invest 92: 1366-1372, 1993.
274. Wu Y, Wu G, Qi X, Lin H, Qian H, Shen J, and Lin S. Protein kinase C beta inhibitor LY333531 attenuates intercellular adhesion molecule-1 and monocyte chemotactic protein-1 expression in the kidney in diabetic rats. J Pharmacol Sci 101: 335-343, 2006.
275. Xia L, Wang H, Goldberg HJ, Munk S, Fantus IG, and Whiteside CI. Mesangial cell NADPH oxidase upregulation in high glucose is protein kinase C dependent and required for collagen IV expression. Am J Physiol Renal Physiol 290: F345-F356, 2006.
276. Xiao H, Li Y, Qi J, Wang H, and Liu K. Peroxynitrite plays a key role in glomerular lesions in diabetic rats. J Nephrol 22: 800-808, 2009.
277. Xu Y, Ruan S, Xie H, and Lin J. Role of LOX-1 in Ang II-induced oxidative functional damage in renal tubular epithelial cells. Int J Mol Med 26: 679-690, 2010.
278. Yang S, Zhang Y, Ries W, and Key L. Expression of Nox4 in osteoclasts. J Cell Biochem 92: 238-248, 2004.
279. Yano M, Hasegawa G, Ishii M, Yamasaki M, Fukui M, Nakamura N, and Yoshikawa T. Short-term exposure of high glucose concentration induces generation of reactive oxygen species in endothelial cells: implication for the oxidative stress associated with postprandial hyperglycemia. Redox Report 9: 111-116, 2004.
280. Yogi A, Mercure C, Touyz J, Callera GE, Montezano AC, Aranha AB, Tostes RC, Reudelhuber T, and Touyz RM. Renal redox-sensitive signaling, but not blood pressure, is attenuated by Nox1 knockout in angiotensin II-dependent chronic hypertension. Hypertension 51: 500-506, 2008.
281. Yong R, Chen XM, Shen S, Vijayaraj S, Ma Q, Pollock CA, and Saad S. Plumbagin ameliorates diabetic nephropathy via interruption of pathways that include NOX4 signalling. PLoS One 8: e73428, 2013.
282. You YH, Okada S, Ly S, Jandeleit-Dahm K, Barit D, Namikoshi T, and Sharma K. Role of Nox2 in diabetic kidney disease. Am J Physiol Renal Physiol 304: F840-F848, 2013.
283. You YH, Quach T, Saito R, Pham J, and Sharma K. Metabolomics reveals a key role for fumarate in mediating the effects of NADPH oxidase 4 in diabetic kidney disease. J Am Soc Nephrol 27: 466-481, 2016.
284. Youn JY, Gao L, and Cai H. The p47phox-and NADPH oxidase organiser 1 (NOXO1)-dependent activation of NADPH oxidase 1 (NOX1) mediates endothelial nitric oxide synthase (eNOS) uncoupling and endothelial dysfunction in a streptozotocin-induced murine model of diabetes. Diabetologia 55: 2069-2079, 2012.
285. Yu P, Han W, Villar VA, Yang Y, Lu Q, Lee H, Li F, Quinn MT, Gildea JJ, Felder RA, and Jose PA. Unique role of NADPH oxidase 5 in oxidative stress in human renal proximal tubule cells. Redox Biol 2: 570-579, 2014.
286. Yue J andMulder KM. Requirement of Ras/MAPKpathway activation by transforming growth factor b for transforming growth factor b1 production in aSmad-dependent pathway. J Biol Chem 275: 30765-30773, 2000.
287. Zhang J, Chandrashekar K, Lu Y, Duan Y, Qu P, Wei J, Juncos LA, and Liu R. Enhanced expression and activity of Nox2 and Nox4 in the macula densa in ANG II-induced hypertensive mice. Am J Physiol Renal Physiol 306: F344-F350, 2014.
288. Zhang M, Brewer AC, Schroder K, Santos CX, Grieve DJ, Wang M, Anilkumar N, Yu B, Dong X, Walker SJ, Brandes RP, and Shah AM. NADPH oxidase-4 mediates protection against chronic load-induced stress in mouse hearts by enhancing angiogenesis. Proc Natl Acad Sci U S A 107: 18121-18126, 2010.
289. ZhangR, Harding P, Garvin JL, JuncosR, PetersonE, Juncos LA, and Liu R. Isoforms and functions of NAD(P)H oxidase at the macula densa. Hypertension 53: 556-563, 2009.
290. Zhao QD, Viswanadhapalli S, Williams P, Shi Q, Tan C, Yi X, Bhandari B, and Abboud HE. NADPH oxidase 4 induces cardiac fibrosis and hypertrophy through activating Akt/mTOR and NFkappaB signaling pathways. Circulation 131: 643-655, 2015.
291. Zheng H, Whitman SA, Wu W, Wondrak GT, Wong PK, Fang D, and Zhang DD. Therapeutic potential of Nrf2 activators in streptozotocin-induced diabetic nephropathy. Diabetes 60: 3055-3066, 2011.
292. Zhou G, Wang Y, He P, and Li D. Probucol inhibited Nox2 expression and attenuated podocyte injury in type 2 diabetic nephropathy of db/db mice. Biol Pharm Bull 36: 1883-1890, 2013.
293. Zhou R, Yazdi AS, Menu P, and Tschopp J. A role for mitochondria in NLRP3 inflammasome activation. Nature 469: 221-225, 2011.
294. Ziyadeh FN. Mediators of diabetic renal disease: the case for TGF-b as the major mediator. J Am Soc Nephrol 15: S55-S57, 2004.
295. Zuo X, Tian C, Zhao N, Ren W, Meng Y, Jin X, Zhang Y, Ding S, Ying C, and Ye X. Tea polyphenols alleviate high fat and high glucose-induced endothelial hyperpermeability by attenuating ROS production via NADPH oxidase pathway. BMC Res Notes 7: 120, 2014.