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Journal of Diabetes Research
Volume 2017 (2017), Article ID 3797802, 14 pages
https://doi.org/10.1155/2017/3797802
Review Article

Role of Nuclear Factor Erythroid 2-Related Factor 2 in Diabetic Nephropathy

1Department of Nephrology, The Second Hospital of Jilin University, Changchun, Jilin 130041, China
2Department of Gynaecology and Obstetrics, The Second Hospital of Jilin University, Changchun, Jilin 130041, China
3Department of Cardiology, The First Hospital of Jilin University, Changchun, Jilin 130031, China

Correspondence should be addressed to Bing Du and Ping Luo

Received 19 December 2016; Revised 9 February 2017; Accepted 13 March 2017; Published 23 April 2017

Academic Editor: Wei J. Liu

Copyright © 2017 Wenpeng Cui 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. M. Haneda, K. Utsunomiya, D. Koya et al., “A new classification of diabetic nephropathy 2014: a report from Joint Committee on Diabetic Nephropathy,” Clinical and Experimental Nephrology, vol. 19, no. 1, pp. 1–5, 2015. View at Publisher · View at Google Scholar · View at Scopus
  2. H. Gallagher and R. J. Suckling, “Diabetic nephropathy: where are we on the journey from pathophysiology to treatment?” Diabetes, Obesity & Metabolism, vol. 18, no. 7, pp. 641–647, 2016. View at Publisher · View at Google Scholar · View at Scopus
  3. A. G. Miranda-Diaz, L. Pazarin-Villasenor, F. G. Yanowsky-Escatell, and J. Andrade-Sierra, “Oxidative stress in diabetic nephropathy with early chronic kidney disease,” Journal of Diabetes Research, vol. 2016, no. 6, p. 7047238, 2016. View at Publisher · View at Google Scholar · View at Scopus
  4. M. K. Arora and U. K. Singh, “Oxidative stress: meeting multiple targets in pathogenesis of diabetic nephropathy,” Current Drug Targets, vol. 15, no. 5, pp. 531–538, 2014. View at Publisher · View at Google Scholar · View at Scopus
  5. W. Cui, Y. Bai, P. Luo, L. Miao, and L. Cai, “Preventive and therapeutic effects of MG132 by activating Nrf2-ARE signaling pathway on oxidative stress-induced cardiovascular and renal injury,” Oxidative Medicine and Cellular Longevity, vol. 2013, no. 3, p. 306073, 2013. View at Publisher · View at Google Scholar · View at Scopus
  6. J. A. Johnson, D. A. Johnson, A. D. Kraft et al., “The Nrf2-ARE pathway: an indicator and modulator of oxidative stress in neurodegeneration,” Annals of the new York Academy of Sciences, vol. 1147, no. 12, pp. 61–69, 2008. View at Publisher · View at Google Scholar · View at Scopus
  7. Y. Kaya, A. Cebi, N. Soylemez, H. Demir, H. H. Alp, and E. Bakan, “Correlations between oxidative DNA damage, oxidative stress and coenzyme Q10 in patients with coronary artery disease,” International Journal of Medical Sciences, vol. 9, no. 8, pp. 621–626, 2012. View at Publisher · View at Google Scholar · View at Scopus
  8. N. J. Pillon, M. L. Croze, R. E. Vella, L. Soulere, M. Lagarde, and C. O. Soulage, “The lipid peroxidation by-product 4-hydroxy-2-nonenal (4-HNE) induces insulin resistance in skeletal muscle through both carbonyl and oxidative stress,” Endocrinology, vol. 153, no. 5, pp. 2099–2111, 2012. View at Publisher · View at Google Scholar · View at Scopus
  9. P. Piomboni, A. Stendardi, L. Gambera et al., “Protein modification as oxidative stress marker in normal and pathological human seminal plasma,” Redox Report, vol. 17, no. 5, pp. 227–232, 2012. View at Publisher · View at Google Scholar · View at Scopus
  10. D. A. Abed, M. Goldstein, H. Albanyan, H. Jin, and L. Hu, “Discovery of direct inhibitors of Keap1-Nrf2 protein-protein interaction as potential therapeutic and preventive agents,” Acta Pharmaceutica Sinica B, vol. 5, no. 4, pp. 285–299, 2015. View at Publisher · View at Google Scholar · View at Scopus
  11. N. Kashihara, Y. Haruna, V. K. Kondeti, and Y. S. Kanwar, “Oxidative stress in diabetic nephropathy,” Current Medicinal Chemistry, vol. 17, no. 34, pp. 4256–4269, 2010. View at Publisher · View at Google Scholar · View at Scopus
  12. N. Vasavada and R. Agarwal, “Role of oxidative stress in diabetic nephropathy,” Advances in Chronic Kidney Disease, vol. 12, no. 2, pp. 146–154, 2005. View at Publisher · View at Google Scholar · View at Scopus
  13. L. Kishore, N. Kaur, and R. Singh, “Renoprotective effect of Bacopa monnieri via inhibition of advanced glycation end products and oxidative stress in STZ-nicotinamide-induced diabetic nephropathy,” Renal Failure, vol. 38, no. 9, pp. 1528–1544, 2016. View at Publisher · View at Google Scholar
  14. S. Ahmed, N. Mundhe, M. Borgohain et al., “Diosmin modulates the NF-kB signal transduction pathways and downregulation of various oxidative stress markers in alloxan-induced diabetic nephropathy,” Inflammation, vol. 39, no. 5, pp. 1783–1797, 2016. View at Publisher · View at Google Scholar · View at Scopus
  15. F. Bahmani, M. Kia, A. Soleimani, A. A. Mohammadi, and Z. Asemi, “The effects of selenium supplementation on biomarkers of inflammation and oxidative stress in patients with diabetic nephropathy: a randomised, double-blind, placebo-controlled trial,” The British Journal of Nutrition, vol. 116, no. 7, pp. 1222–1228, 2016. View at Publisher · View at Google Scholar
  16. P. G. Khatami, A. Soleimani, N. Sharifi, E. Aghadavod, and Z. Asemi, “The effects of high-dose vitamin E supplementation on biomarkers of kidney injury, inflammation, and oxidative stress in patients with diabetic nephropathy: a randomized, double-blind, placebo-controlled trial,” Journal of Clinical Lipidology, vol. 10, no. 4, pp. 922–929, 2016. View at Publisher · View at Google Scholar · View at Scopus
  17. S. Ogawa, T. Mori, K. Nako, T. Kato, K. Takeuchi, and S. Ito, “Angiotensin II type 1 receptor blockers reduce urinary oxidative stress markers in hypertensive diabetic nephropathy,” Hypertension, vol. 47, no. 4, pp. 699–705, 2006. View at Publisher · View at Google Scholar · View at Scopus
  18. P. Moi, K. Chan, I. Asunis, A. Cao, and Y. W. Kan, “Isolation of NF-E2-related factor 2 (Nrf2), a NF-E2-like basic leucine zipper transcriptional activator that binds to the tandem NF-E2/AP1 repeat of the beta-globin locus control region,” Proceedings of the National Academy of Sciences of the United States of America, vol. 91, no. 21, pp. 9926–9930, 1994. View at Publisher · View at Google Scholar · View at Scopus
  19. K. Itoh, J. Mimura, and M. Yamamoto, “Discovery of the negative regulator of Nrf2, Keap1: a historical overview,” Antioxidants & Redox Signaling, vol. 13, no. 11, pp. 1665–1678, 2010. View at Publisher · View at Google Scholar · View at Scopus
  20. Y. S. Keum and B. Y. Choi, “Molecular and chemical regulation of the Keap1-Nrf2 signaling pathway,” Molecules, vol. 19, no. 7, pp. 10074–10089, 2014. View at Publisher · View at Google Scholar · View at Scopus
  21. K. Itoh, T. Chiba, S. Takahashi et al., “An Nrf2/small Maf heterodimer mediates the induction of phase II detoxifying enzyme genes through antioxidant response elements,” Biochemical and Biophysical Research Communications, vol. 236, no. 2, pp. 313–322, 1997. View at Publisher · View at Google Scholar · View at Scopus
  22. A. K. Jain, D. A. Bloom, and A. K. Jaiswal, “Nuclear import and export signals in control of Nrf2,” The Journal of Biological Chemistry, vol. 280, no. 32, pp. 29158–29168, 2005. View at Publisher · View at Google Scholar · View at Scopus
  23. K. Itoh, K. I. Tong, and M. Yamamoto, “Molecular mechanism activating Nrf2-Keap1 pathway in regulation of adaptive response to electrophiles,” Free Radical Biology & Medicine, vol. 36, no. 10, pp. 1208–1213, 2004. View at Publisher · View at Google Scholar · View at Scopus
  24. K. I. Tong, Y. Katoh, H. Kusunoki, K. Itoh, T. Tanaka, and M. Yamamoto, “Keap1 recruits Neh2 through binding to ETGE and DLG motifs: characterization of the two-site molecular recognition model,” Molecular and Cellular Biology, vol. 26, no. 8, pp. 2887–2900, 2006. View at Publisher · View at Google Scholar · View at Scopus
  25. K. Itoh, N. Wakabayashi, Y. Katoh et al., “Keap1 represses nuclear activation of antioxidant responsive elements by Nrf2 through binding to the amino-terminal Neh2 domain,” Genes & Development, vol. 13, no. 1, pp. 76–86, 1999. View at Publisher · View at Google Scholar
  26. D. D. Zhang, S. C. Lo, J. V. Cross, D. J. Templeton, and M. Hannink, “Keap1 is a redox-regulated substrate adaptor protein for a Cul3-dependent ubiquitin ligase complex,” Molecular and Cellular Biology, vol. 24, no. 24, pp. 10941–10953, 2004. View at Publisher · View at Google Scholar · View at Scopus
  27. Y. Katoh, K. Itoh, E. Yoshida, M. Miyagishi, A. Fukamizu, and M. Yamamoto, “Two domains of Nrf2 cooperatively bind CBP, a CREB binding protein, and synergistically activate transcription,” Genes to Cells : Devoted to Molecular & Cellular Mechanisms, vol. 6, no. 10, pp. 857–868, 2001. View at Publisher · View at Google Scholar · View at Scopus
  28. M. McMahon, N. Thomas, K. Itoh, M. Yamamoto, and J. D. Hayes, “Redox-regulated turnover of Nrf2 is determined by at least two separate protein domains, the redox-sensitive Neh2 degron and the redox-insensitive Neh6 degron,” The Journal of Biological Chemistry, vol. 279, no. 30, pp. 31556–31567, 2004. View at Publisher · View at Google Scholar · View at Scopus
  29. H. Wang, K. Liu, M. Geng et al., “RXRalpha inhibits the NRF2-ARE signaling pathway through a direct interaction with the Neh7 domain of NRF2,” Cancer Research, vol. 73, no. 10, pp. 3097–3108, 2013. View at Publisher · View at Google Scholar · View at Scopus
  30. N. Wakabayashi, A. T. Dinkova-Kostova, W. D. Holtzclaw et al., “Protection against electrophile and oxidant stress by induction of the phase 2 response: fate of cysteines of the Keap1 sensor modified by inducers,” Proceedings of the National Academy of Sciences of the United States of America, vol. 101, no. 7, pp. 2040–2045, 2004. View at Publisher · View at Google Scholar · View at Scopus
  31. L. M. Zipper and R. T. Mulcahy, “The Keap1 BTB/POZ dimerization function is required to sequester Nrf2 in cytoplasm,” The Journal of Biological Chemistry, vol. 277, no. 39, pp. 36544–36552, 2002. View at Publisher · View at Google Scholar · View at Scopus
  32. N. Chauhan, L. Chaunsali, P. Deshmukh, and B. Padmanabhan, “Analysis of dimerization of BTB-IVR domains of Keap1 and its interaction with Cul3, by molecular modeling,” Bioinformation, vol. 9, no. 9, pp. 450–455, 2013. View at Publisher · View at Google Scholar
  33. 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. View at Publisher · View at Google Scholar · View at Scopus
  34. W. Hur and N. S. Gray, “Small molecule modulators of antioxidant response pathway,” Current Opinion in Chemical Biology, vol. 15, no. 1, pp. 162–173, 2011. View at Publisher · View at Google Scholar · View at Scopus
  35. R. Saito, T. Suzuki, K. Hiramoto et al., “Characterizations of three major cysteine sensors of Keap1 in stress response,” Molecular and Cellular Biology, vol. 36, no. 2, pp. 271–284, 2015. View at Publisher · View at Google Scholar · View at Scopus
  36. K. Takaya, T. Suzuki, H. Motohashi et al., “Validation of the multiple sensor mechanism of the Keap1-Nrf2 system,” Free Radical Biology & Medicine, vol. 53, no. 4, pp. 817–827, 2012. View at Publisher · View at Google Scholar · View at Scopus
  37. A. Uruno and H. Motohashi, “The Keap1-Nrf2 system as an in vivo sensor for electrophiles,” Nitric Oxide : Biology and Chemistry, vol. 25, no. 2, pp. 153–160, 2011. View at Publisher · View at Google Scholar · View at Scopus
  38. J. D. Hayes and M. McMahon, “NRF2 and KEAP1 mutations: permanent activation of an adaptive response in cancer,” Trends in Biochemical Sciences, vol. 34, no. 4, pp. 176–188, 2009. View at Publisher · View at Google Scholar · View at Scopus
  39. Y. Katoh, K. Iida, M. I. Kang et al., “Evolutionary conserved N-terminal domain of Nrf2 is essential for the Keap1-mediated degradation of the protein by proteasome,” Archives of Biochemistry and Biophysics, vol. 433, no. 2, pp. 342–350, 2005. View at Publisher · View at Google Scholar · View at Scopus
  40. D. Stewart, E. Killeen, R. Naquin, S. Alam, and J. Alam, “Degradation of transcription factor Nrf2 via the ubiquitin-proteasome pathway and stabilization by cadmium,” The Journal of Biological Chemistry, vol. 278, no. 4, pp. 2396–2402, 2003. View at Publisher · View at Google Scholar · View at Scopus
  41. K. J. Min, J. H. Kim, I. Jou, and E. H. Joe, “Adenosine induces hemeoxygenase-1 expression in microglia through the activation of phosphatidylinositol 3-kinase and nuclear factor E2-related factor 2,” Glia, vol. 56, no. 9, pp. 1028–1037, 2008. View at Publisher · View at Google Scholar · View at Scopus
  42. S. Kalayarasan, P. N. Prabhu, N. Sriram, R. Manikandan, M. Arumugam, and G. Sudhandiran, “Diallyl sulfide enhances antioxidants and inhibits inflammation through the activation of Nrf2 against gentamicin-induced nephrotoxicity in Wistar rats,” European Journal of Pharmacology, vol. 606, no. 1-3, pp. 162–171, 2009. View at Publisher · View at Google Scholar · View at Scopus
  43. S. Ruiz, P. E. Pergola, R. A. Zager, and N. D. Vaziri, “Targeting the transcription factor Nrf2 to ameliorate oxidative stress and inflammation in chronic kidney disease,” Kidney International, vol. 83, no. 6, pp. 1029–1041, 2013. View at Publisher · View at Google Scholar · View at Scopus
  44. B. Harder, T. Jiang, T. Wu et al., “Molecular mechanisms of Nrf2 regulation and how these influence chemical modulation for disease intervention,” Biochemical Society Transactions, vol. 43, no. 4, pp. 680–686, 2015. View at Publisher · View at Google Scholar · View at Scopus
  45. M. K. Kwak, K. Itoh, M. Yamamoto, and T. W. Kensler, “Enhanced expression of the transcription factor Nrf2 by cancer chemopreventive agents: role of antioxidant response element-like sequences in the nrf2 promoter,” Molecular and Cellular Biology, vol. 22, no. 9, pp. 2883–2892, 2002. View at Publisher · View at Google Scholar · View at Scopus
  46. X. Cheng, C. H. Ku, and R. C. Siow, “Regulation of the Nrf2 antioxidant pathway by microRNAs: new players in micromanaging redox homeostasis,” Free Radical Biology & Medicine, vol. 64, no. 9, pp. 4–11, 2013. View at Publisher · View at Google Scholar · View at Scopus
  47. M. Yang, Y. Yao, G. Eades, Y. Zhang, and Q. Zhou, “MiR-28 regulates Nrf2 expression through a Keap1-independent mechanism,” Breast Cancer Research and Treatment, vol. 129, no. 3, pp. 983–991, 2011. View at Publisher · View at Google Scholar · View at Scopus
  48. N. Li, S. Muthusamy, R. Liang, H. Sarojini, and E. Wang, “Increased expression of miR-34a and miR-93 in rat liver during aging, and their impact on the expression of Mgst1 and Sirt1,” Mechanisms of Ageing and Development, vol. 132, no. 3, pp. 75–85, 2011. View at Publisher · View at Google Scholar · View at Scopus
  49. A. Stachurska, M. Ciesla, M. Kozakowska et al., “Cross-talk between microRNAs, nuclear factor E2-related factor 2, and heme oxygenase-1 in ochratoxin A-induced toxic effects in renal proximal tubular epithelial cells,” Molecular Nutrition & Food Research, vol. 57, no. 3, pp. 504–515, 2013. View at Publisher · View at Google Scholar · View at Scopus
  50. G. Eades, M. Yang, Y. Yao, Y. Zhang, and Q. Zhou, “miR-200a regulates Nrf2 activation by targeting Keap1 mRNA in breast cancer cells,” The Journal of Biological Chemistry, vol. 286, no. 47, pp. 40725–40733, 2011. View at Publisher · View at Google Scholar · View at Scopus
  51. T. O. Khor, Y. Huang, T. Y. Wu, L. Shu, J. Lee, and A. N. Kong, “Pharmacodynamics of curcumin as DNA hypomethylation agent in restoring the expression of Nrf2 via promoter CpGs demethylation,” Biochemical Pharmacology, vol. 82, no. 9, pp. 1073–1078, 2011. View at Publisher · View at Google Scholar · View at Scopus
  52. C. Zhang, Z. Y. Su, T. O. Khor, L. Shu, and A. N. Kong, “Sulforaphane enhances Nrf2 expression in prostate cancer TRAMP C1 cells through epigenetic regulation,” Biochemical Pharmacology, vol. 85, no. 9, pp. 1398–1404, 2013. View at Publisher · View at Google Scholar · View at Scopus
  53. F. Correa, C. Mallard, M. Nilsson, and M. Sandberg, “Activated microglia decrease histone acetylation and Nrf2-inducible anti-oxidant defence in astrocytes: restoring effects of inhibitors of HDACs, p38 MAPK and GSK3beta,” Neurobiology of Disease, vol. 44, no. 1, pp. 142–151, 2011. View at Publisher · View at Google Scholar · View at Scopus
  54. Z. Li, L. Xu, N. Tang et al., “The polycomb group protein EZH2 inhibits lung cancer cell growth by repressing the transcription factor Nrf2,” FEBS Letters, vol. 588, no. 17, pp. 3000–3007, 2014. View at Publisher · View at Google Scholar · View at Scopus
  55. Y. Guo, S. Yu, C. Zhang, and A. N. Kong, “Epigenetic regulation of Keap1-Nrf2 signaling,” Free Radical Biology & Medicine, vol. 88, no. Pt B, pp. 337–349, 2015. View at Publisher · View at Google Scholar · View at Scopus
  56. N. F. Villeneuve, A. Lau, and D. D. Zhang, “Regulation of the Nrf2-Keap1 antioxidant response by the ubiquitin proteasome system: an insight into cullin-ring ubiquitin ligases,” Antioxidants & Redox Signaling, vol. 13, no. 11, pp. 1699–1712, 2010. View at Publisher · View at Google Scholar · View at Scopus
  57. W. Cui, B. Li, Y. Bai et al., “Potential role for Nrf2 activation in the therapeutic effect of MG132 on diabetic nephropathy in OVE26 diabetic mice,” American Journal of Physiology Endocrinology and Metabolism, vol. 304, no. 1, pp. E87–E99, 2013. View at Publisher · View at Google Scholar
  58. A. Lau, X. J. Wang, F. Zhao et al., “A noncanonical mechanism of Nrf2 activation by autophagy deficiency: direct interaction between Keap1 and p62,” Molecular and Cellular Biology, vol. 30, no. 13, pp. 3275–3285, 2010. View at Publisher · View at Google Scholar · View at Scopus
  59. H. C. Huang, T. Nguyen, and C. B. Pickett, “Phosphorylation of Nrf2 at Ser-40 by protein kinase C regulates antioxidant response element-mediated transcription,” The Journal of Biological Chemistry, vol. 277, no. 45, pp. 42769–42774, 2002. View at Publisher · View at Google Scholar · View at Scopus
  60. M. Miyazawa and Y. Tsuji, “Evidence for a novel antioxidant function and isoform-specific regulation of the human p66Shc gene,” Molecular Biology of the Cell, vol. 25, no. 13, pp. 2116–2127, 2014. View at Publisher · View at Google Scholar · View at Scopus
  61. T. Miyata, N. Suzuki, and C. van Ypersele de Strihou, “Diabetic nephropathy: are there new and potentially promising therapies targeting oxygen biology?” Kidney International, vol. 84, no. 4, pp. 693–702, 2013. View at Publisher · View at Google Scholar · View at Scopus
  62. Q. Sun, Z. Y. Shen, Q. T. Meng, H. Z. Liu, W. N. Duan, and Z. Y. Xia, “The role of DJ-1/Nrf2 pathway in the pathogenesis of diabetic nephropathy in rats,” Renal Failure, vol. 38, no. 2, pp. 294–304, 2016. View at Google Scholar
  63. K. Yoh, A. Hirayama, K. Ishizaki et al., “Hyperglycemia induces oxidative and nitrosative stress and increases renal functional impairment in Nrf2-deficient mice,” Genes to Cells : Devoted to Molecular & Cellular Mechanisms, vol. 13, no. 11, pp. 1159–1170, 2008. View at Publisher · View at Google Scholar · View at Scopus
  64. T. Jiang, Z. Huang, Y. Lin, Z. Zhang, D. Fang, and D. D. Zhang, “The protective role of Nrf2 in streptozotocin-induced diabetic nephropathy,” Diabetes, vol. 59, no. 4, pp. 850–860, 2010. View at Publisher · View at Google Scholar · View at Scopus
  65. B. H. Choi, K. S. Kang, and M. K. Kwak, “Effect of redox modulating NRF2 activators on chronic kidney disease,” Molecules, vol. 19, no. 8, pp. 12727–12759, 2014. View at Publisher · View at Google Scholar · View at Scopus
  66. N. Wakabayashi, K. Itoh, J. Wakabayashi et al., “Keap1-null mutation leads to postnatal lethality due to constitutive Nrf2 activation,” Nature Genetics, vol. 35, no. 3, pp. 238–245, 2003. View at Publisher · View at Google Scholar · View at Scopus
  67. V. R. More, J. Xu, P. C. Shimpi et al., “Keap1 knockdown increases markers of metabolic syndrome after long-term high fat diet feeding,” Free Radical Biology & Medicine, vol. 61, no. 8, pp. 85–94, 2013. View at Publisher · View at Google Scholar · View at Scopus
  68. Y. K. Zhang, K. C. Wu, J. Liu, and C. D. Klaassen, “Nrf2 deficiency improves glucose tolerance in mice fed a high-fat diet,” Toxicology and Applied Pharmacology, vol. 264, no. 3, pp. 305–314, 2012. View at Publisher · View at Google Scholar · View at Scopus
  69. J. Xu, S. R. Kulkarni, A. C. Donepudi, V. R. More, and A. L. Slitt, “Enhanced Nrf2 activity worsens insulin resistance, impairs lipid accumulation in adipose tissue, and increases hepatic steatosis in leptin-deficient mice,” Diabetes, vol. 61, no. 12, pp. 3208–3218, 2012. View at Publisher · View at Google Scholar · View at Scopus
  70. M. S. Yates, Q. T. Tran, P. M. Dolan et al., “Genetic versus chemoprotective activation of Nrf2 signaling: overlapping yet distinct gene expression profiles between Keap1 knockout and triterpenoid-treated mice,” Carcinogenesis, vol. 30, no. 6, pp. 1024–1031, 2009. View at Publisher · View at Google Scholar · View at Scopus
  71. X. Wang, X. Zhao, T. Feng, G. Jin, and Z. Li, “Rutin prevents high glucose-induced renal glomerular endothelial hyperpermeability by inhibiting the ROS/Rhoa/ROCK signaling pathway,” Planta Medica, vol. 82, no. 14, pp. 1252–1257, 2016. View at Publisher · View at Google Scholar · View at Scopus
  72. X. Zhang, H. He, D. Liang et al., “Protective effects of berberine on renal injury in streptozotocin (STZ)-induced diabetic mice,” International Journal of Molecular Sciences, vol. 17, no. 8, p. 1327, 2016. View at Publisher · View at Google Scholar · View at Scopus
  73. W. Gong, C. Chen, F. Xiong et al., “CKIP-1 ameliorates high glucose-induced expression of fibronectin and intercellular cell adhesion molecule-1 by activating the Nrf2/ARE pathway in glomerular mesangial cells,” Biochemical Pharmacology, vol. 116, no. 9, pp. 140–152, 2016. View at Publisher · View at Google Scholar · View at Scopus
  74. M. M. Hussein and M. K. Mahfouz, “Effect of resveratrol and rosuvastatin on experimental diabetic nephropathy in rats,” Biomedicine & Pharmacotherapy = Biomedecine & Pharmacotherapie, vol. 82, no. 8, pp. 685–692, 2016. View at Publisher · View at Google Scholar · View at Scopus
  75. P. Wu, Y. Yan, L. L. Ma et al., “Effects of the Nrf2 protein modulator salvianolic acid A alone or combined with metformin on diabetes-associated macrovascular and renal injury,” The Journal of Biological Chemistry, vol. 291, no. 42, pp. 22288–22301, 2016. View at Publisher · View at Google Scholar
  76. Q. Yin, Y. Xia, and G. Wang, “Sinomenine alleviates high glucose-induced renal glomerular endothelial hyperpermeability by inhibiting the activation of RhoA/ROCK signaling pathway,” Biochemical and Biophysical Research Communications, vol. 477, no. 4, pp. 881–886, 2016. View at Publisher · View at Google Scholar · View at Scopus
  77. M. Raish, A. Ahmad, B. L. Jan et al., “Momordica charantia polysaccharides mitigate the progression of STZ induced diabetic nephropathy in rats,” International Journal of Biological Macromolecules, vol. 91, no. 10, pp. 394–399, 2016. View at Publisher · View at Google Scholar · View at Scopus
  78. B. H. Kim, E. S. Lee, R. Choi et al., “Protective effects of curcumin on renal oxidative stress and lipid metabolism in a rat model of type 2 diabetic nephropathy,” Yonsei Medical Journal, vol. 57, no. 3, pp. 664–673, 2016. View at Publisher · View at Google Scholar · View at Scopus
  79. Y. Yang, G. Chen, X. Cheng et al., “Therapeutic potential of digitoflavone on diabetic nephropathy: nuclear factor erythroid 2-related factor 2-dependent anti-oxidant and anti-inflammatory effect,” Scientific Reports, vol. 5, no. 6, p. 12377, 2015. View at Publisher · View at Google Scholar · View at Scopus
  80. X. Zhang, D. Liang, L. Guo et al., “Curcumin protects renal tubular epithelial cells from high glucose-induced epithelial-to-mesenchymal transition through Nrf2-mediated upregulation of heme oxygenase-1,” Molecular Medicine Reports, vol. 12, no. 1, pp. 1347–1355, 2015. View at Publisher · View at Google Scholar · View at Scopus
  81. L. Zhou, D. Y. Xu, W. G. Sha et al., “High glucose induces renal tubular epithelial injury via Sirt1/NF-kappaB/microR-29/Keap1 signal pathway,” Journal of Translational Medicine, vol. 13, no. 11, p. 352, 2015. View at Publisher · View at Google Scholar · View at Scopus
  82. S. M. Yang, S. M. Ka, H. L. Wu et al., “Thrombomodulin domain 1 ameliorates diabetic nephropathy in mice via anti-NF-kappaB/NLRP3 inflammasome-mediated inflammation, enhancement of NRF2 antioxidant activity and inhibition of apoptosis,” Diabetologia, vol. 57, no. 2, pp. 424–434, 2014. View at Publisher · View at Google Scholar · View at Scopus
  83. K. Nakai, H. Fujii, K. Kono et al., “Vitamin D activates the Nrf2-Keap1 antioxidant pathway and ameliorates nephropathy in diabetic rats,” American Journal of Hypertension, vol. 27, no. 4, pp. 586–595, 2014. View at Publisher · View at Google Scholar · View at Scopus
  84. B. Jiang, L. Guo, B. Y. Li et al., “Resveratrol attenuates early diabetic nephropathy by down-regulating glutathione s-transferases Mu in diabetic rats,” Journal of Medicinal Food, vol. 16, no. 6, pp. 481–486, 2013. View at Publisher · View at Google Scholar · View at Scopus
  85. W. Cui, Y. Bai, X. Miao et al., “Prevention of diabetic nephropathy by sulforaphane: possible role of Nrf2 upregulation and activation,” Oxidative Medicine and Cellular Longevity, vol. 2012, no. 9, p. 821936, 2012. View at Publisher · View at Google Scholar · View at Scopus
  86. H. Zheng, S. A. Whitman, W. Wu et al., “Therapeutic potential of Nrf2 activators in streptozotocin-induced diabetic nephropathy,” Diabetes, vol. 60, no. 11, pp. 3055–3066, 2011. View at Publisher · View at Google Scholar · View at Scopus
  87. P. Palsamy and S. Subramanian, “Resveratrol protects diabetic kidney by attenuating hyperglycemia-mediated oxidative stress and renal inflammatory cytokines via Nrf2-Keap1 signaling,” Biochimica et Biophysica Acta, vol. 1812, no. 7, pp. 719–731, 2011. View at Publisher · View at Google Scholar · View at Scopus
  88. Z. F. Luo, B. Feng, J. Mu et al., “Effects of 4-phenylbutyric acid on the process and development of diabetic nephropathy induced in rats by streptozotocin: regulation of endoplasmic reticulum stress-oxidative activation,” Toxicology and Applied Pharmacology, vol. 246, no. 1-2, pp. 49–57, 2010. View at Publisher · View at Google Scholar · View at Scopus
  89. H. Wu, L. Kong, Y. Cheng et al., “Metallothionein plays a prominent role in the prevention of diabetic nephropathy by sulforaphane via up-regulation of Nrf2,” Free Radical Biology & Medicine, vol. 89, no. 12, pp. 431–442, 2015. View at Publisher · View at Google Scholar · View at Scopus
  90. W. Dong, Y. Jia, X. Liu et al., “Sodium butyrate activates NRF2 to ameliorate diabetic nephropathy possibly via inhibition of HDAC,” The Journal of Endocrinology, vol. 232, no. 1, pp. 71–83, 2017. View at Publisher · View at Google Scholar
  91. Z. Chen, X. Xie, J. Huang et al., “Connexin43 regulates high glucose-induced expression of fibronectin, ICAM-1 and TGF-beta1 via Nrf2/ARE pathway in glomerular mesangial cells,” Free Radical Biology & Medicine, vol. 102, no. 1, pp. 77–86, 2017. View at Publisher · View at Google Scholar
  92. K. Shahzad, F. Bock, M. M. Al-Dabet et al., “Stabilization of endogenous Nrf2 by minocycline protects against Nlrp3-inflammasome induced diabetic nephropathy,” Scientific Reports, vol. 6, no. 10, p. 34228, 2016. View at Publisher · View at Google Scholar
  93. H. Wu, L. Kong, Y. Tan et al., “C66 ameliorates diabetic nephropathy in mice by both upregulating NRF2 function via increase in miR-200a and inhibiting miR-21,” Diabetologia, vol. 59, no. 7, pp. 1558–1568, 2016. View at Publisher · View at Google Scholar · View at Scopus
  94. A. S. Arellano-Buendia, M. Tostado-Gonzalez, F. E. Garcia-Arroyo et al., “Anti-inflammatory therapy modulates Nrf2-Keap1 in kidney from rats with diabetes,” Oxidative Medicine and Cellular Longevity, vol. 2016, no. 2, p. 4693801, 2016. View at Publisher · View at Google Scholar · View at Scopus
  95. Y. Cheng, J. Zhang, W. Guo et al., “Up-regulation of Nrf2 is involved in FGF21-mediated fenofibrate protection against type 1 diabetic nephropathy,” Free Radical Biology & Medicine, vol. 93, no. 4, pp. 94–109, 2016. View at Publisher · View at Google Scholar · View at Scopus
  96. G. Shang, X. Tang, P. Gao et al., “Sulforaphane attenuation of experimental diabetic nephropathy involves GSK-3 beta/Fyn/Nrf2 signaling pathway,” The Journal of Nutritional Biochemistry, vol. 26, no. 6, pp. 596–606, 2015. View at Publisher · View at Google Scholar · View at Scopus
  97. K. Huang, C. Chen, J. Hao et al., “Polydatin promotes Nrf2-ARE anti-oxidative pathway through activating Sirt1 to resist AGEs-induced upregulation of fibronetin and transforming growth factor-beta1 in rat glomerular messangial cells,” Molecular and Cellular Endocrinology, vol. 399, no. 1, pp. 178–189, 2015. View at Publisher · View at Google Scholar · View at Scopus
  98. B. Li, W. Cui, Y. Tan et al., “Zinc is essential for the transcription function of Nrf2 in human renal tubule cells in vitro and mouse kidney in vivo under the diabetic condition,” Journal of Cellular and Molecular Medicine, vol. 18, no. 5, pp. 895–906, 2014. View at Publisher · View at Google Scholar · View at Scopus
  99. X. Zhang, Y. Zhao, Q. Chu, Z. Y. Wang, H. Li, and Z. H. Chi, “Zinc modulates high glucose-induced apoptosis by suppressing oxidative stress in renal tubular epithelial cells,” Biological Trace Element Research, vol. 158, no. 2, pp. 259–267, 2014. View at Publisher · View at Google Scholar · View at Scopus
  100. X. Zhou, Y. Feng, Z. Zhan, and J. Chen, “Hydrogen sulfide alleviates diabetic nephropathy in a streptozotocin-induced diabetic rat model,” The Journal of Biological Chemistry, vol. 289, no. 42, pp. 28827–28834, 2014. View at Publisher · View at Google Scholar · View at Scopus
  101. K. Huang, J. Huang, X. Xie et al., “Sirt1 resists advanced glycation end products-induced expressions of fibronectin and TGF-beta1 by activating the Nrf2/ARE pathway in glomerular mesangial cells,” Free Radical Biology & Medicine, vol. 65, no. 12, pp. 528–540, 2013. View at Publisher · View at Google Scholar · View at Scopus
  102. X. Xing, C. Zhang, M. Shao et al., “Low-dose radiation activates Akt and Nrf2 in the kidney of diabetic mice: a potential mechanism to prevent diabetic nephropathy,” Oxidative Medicine and Cellular Longevity, vol. 2012, no. 11, p. 291087, 2012. View at Publisher · View at Google Scholar · View at Scopus
  103. S. Guoguo, T. Akaike, J. Tao, C. Qi, Z. Nong, and L. Hui, “HGF-mediated inhibition of oxidative stress by 8-nitro-cGMP in high glucose-treated rat mesangial cells,” Free Radical Research, vol. 46, no. 10, pp. 1238–1248, 2012. View at Publisher · View at Google Scholar · View at Scopus
  104. H. Fujita, H. Fujishima, T. Morii et al., “Modulation of renal superoxide dismutase by telmisartan therapy in C57BL/6-Ins2(Akita) diabetic mice,” Hypertension Research : Official Journal of the Japanese Society of Hypertension, vol. 35, no. 2, pp. 213–220, 2012. View at Publisher · View at Google Scholar · View at Scopus
  105. H. Li, L. Zhang, F. Wang et al., “Attenuation of glomerular injury in diabetic mice with tert-butylhydroquinone through nuclear factor erythroid 2-related factor 2-dependent antioxidant gene activation,” American Journal of Nephrology, vol. 33, no. 4, pp. 289–297, 2011. View at Publisher · View at Google Scholar · View at Scopus
  106. Z. F. Luo, W. Qi, B. Feng et al., “Prevention of diabetic nephropathy in rats through enhanced renal antioxidative capacity by inhibition of the proteasome,” Life Sciences, vol. 88, no. 11-12, pp. 512–520, 2011. View at Publisher · View at Google Scholar · View at Scopus
  107. J. Wei, Y. Zhang, Y. Luo et al., “Aldose reductase regulates miR-200a-3p/141-3p to coordinate Keap1-Nrf2, Tgfbeta1/2, and Zeb1/2 signaling in renal mesangial cells and the renal cortex of diabetic mice,” Free Radical Biology & Medicine, vol. 67, no. 2, pp. 91–102, 2014. View at Publisher · View at Google Scholar · View at Scopus
  108. M. C. Haigis and L. P. Guarente, “Mammalian sirtuins—emerging roles in physiology, aging, and calorie restriction,” Genes & Development, vol. 20, no. 21, pp. 2913–2921, 2006. View at Publisher · View at Google Scholar · View at Scopus
  109. D. Yang, X. Tan, Z. Lv et al., “Regulation of Sirt1/Nrf2/TNF-alpha signaling pathway by luteolin is critical to attenuate acute mercuric chloride exposure induced hepatotoxicity,” Scientific Reports, vol. 6, no. 11, p. 37157, 2016. View at Publisher · View at Google Scholar
  110. X. Xia, B. Qu, Y. M. Li et al., “NFAT5 protects astrocytes against oxygen-glucose-serum deprivation/restoration damage via the SIRT1/Nrf2 pathway,” Journal of Molecular Neuroscience : MN, vol. 61, no. 1, pp. 96–104, 2016. View at Publisher · View at Google Scholar
  111. S. A. Shah, M. Khan, M. H. Jo, M. G. Jo, F. U. Amin, and M. O. Kim, “Melatonin stimulates the SIRT1/Nrf2 signaling pathway counteracting lipopolysaccharide (LPS)-induced oxidative stress to rescue postnatal rat brain,” CNS Neuroscience & Therapeutics, vol. 23, no. 1, pp. 33–44, 2016. View at Publisher · View at Google Scholar · View at Scopus
  112. A. Cao, L. Wang, X. Chen et al., “Ursodeoxycholic acid ameliorated diabetic nephropathy by attenuating hyperglycemia-mediated oxidative stress,” Biological & Pharmaceutical Bulletin, vol. 39, no. 8, pp. 1300–1308, 2016. View at Publisher · View at Google Scholar · View at Scopus
  113. C. Wang, C. Li, H. Peng et al., “Activation of the Nrf2-ARE pathway attenuates hyperglycemia-mediated injuries in mouse podocytes,” Cellular Physiology and Biochemistry : International Journal of Experimental Cellular Physiology, Biochemistry, and Pharmacology, vol. 34, no. 3, pp. 891–902, 2014. View at Publisher · View at Google Scholar · View at Scopus
  114. X. Xu, J. Sun, X. Chang et al., “Genetic variants of nuclear factor erythroid-derived 2-like 2 associated with the complications in Han descents with type 2 diabetes mellitus of Northeast China,” Journal of Cellular and Molecular Medicine, vol. 20, no. 11, pp. 2078–2088, 2016. View at Publisher · View at Google Scholar
  115. K. T. Liby, M. M. Yore, and M. B. Sporn, “Triterpenoids and rexinoids as multifunctional agents for the prevention and treatment of cancer,” Nature Reviews Cancer, vol. 7, no. 5, pp. 357–369, 2007. View at Publisher · View at Google Scholar · View at Scopus
  116. K. T. Liby and M. B. Sporn, “Synthetic oleanane triterpenoids: multifunctional drugs with a broad range of applications for prevention and treatment of chronic disease,” Pharmacological Reviews, vol. 64, no. 4, pp. 972–1003, 2012. View at Publisher · View at Google Scholar · View at Scopus
  117. S. Nagaraj, J. I. Youn, H. Weber et al., “Anti-inflammatory triterpenoid blocks immune suppressive function of MDSCs and improves immune response in cancer,” Clinical Cancer Research : An Official Journal of the American Association for Cancer Research, vol. 16, no. 6, pp. 1812–1823, 2010. View at Publisher · View at Google Scholar · View at Scopus
  118. D. S. Hong, R. Kurzrock, J. G. Supko et al., “A phase I first-in-human trial of bardoxolone methyl in patients with advanced solid tumors and lymphomas,” Clinical Cancer Research : An Official Journal of the American Association for Cancer Research, vol. 18, no. 12, pp. 3396–3406, 2012. View at Publisher · View at Google Scholar · View at Scopus
  119. P. E. Pergola, M. Krauth, J. W. Huff et al., “Effect of bardoxolone methyl on kidney function in patients with T2D and stage 3b-4 CKD,” American Journal of Nephrology, vol. 33, no. 5, pp. 469–476, 2011. View at Publisher · View at Google Scholar · View at Scopus
  120. P. E. Pergola, P. Raskin, R. D. Toto et al., “Bardoxolone methyl and kidney function in CKD with type 2 diabetes,” The New England Journal of Medicine, vol. 365, no. 4, pp. 327–336, 2011. View at Publisher · View at Google Scholar · View at Scopus
  121. D. de Zeeuw, T. Akizawa, P. Audhya et al., “Bardoxolone methyl in type 2 diabetes and stage 4 chronic kidney disease,” The New England Journal of Medicine, vol. 369, no. 26, pp. 2492–2503, 2013. View at Publisher · View at Google Scholar · View at Scopus
  122. M. P. Chin, D. Wrolstad, G. L. Bakris et al., “Risk factors for heart failure in patients with type 2 diabetes mellitus and stage 4 chronic kidney disease treated with bardoxolone methyl,” Journal of Cardiac Failure, vol. 20, no. 12, pp. 953–958, 2014. View at Publisher · View at Google Scholar · View at Scopus
  123. M. P. Chin, S. A. Reisman, G. L. Bakris et al., “Mechanisms contributing to adverse cardiovascular events in patients with type 2 diabetes mellitus and stage 4 chronic kidney disease treated with bardoxolone methyl,” American Journal of Nephrology, vol. 39, no. 6, pp. 499–508, 2014. View at Publisher · View at Google Scholar · View at Scopus
  124. S. Abdo, Y. Shi, A. Otoukesh et al., “Catalase overexpression prevents nuclear factor erythroid 2-related factor 2 stimulation of renal angiotensinogen gene expression, hypertension, and kidney injury in diabetic mice,” Diabetes, vol. 63, no. 10, pp. 3483–3496, 2014. View at Publisher · View at Google Scholar · View at Scopus
  125. N. Noori, C. P. Kovesdy, R. Bross et al., “Novel equations to estimate lean body mass in maintenance hemodialysis patients,” American Journal of Kidney Diseases : The Official Journal of the National Kidney Foundation, vol. 57, no. 1, pp. 130–139, 2011. View at Publisher · View at Google Scholar · View at Scopus
  126. S. S. Patel, M. Z. Molnar, J. A. Tayek et al., “Serum creatinine as a marker of muscle mass in chronic kidney disease: results of a cross-sectional study and review of literature,” Journal of Cachexia, Sarcopenia and Muscle, vol. 4, no. 1, pp. 19–29, 2013. View at Publisher · View at Google Scholar · View at Scopus
  127. J. A. Tayek and K. Kalantar-Zadeh, “The extinguished BEACON of bardoxolone: not a Monday morning quarterback story,” American Journal of Nephrology, vol. 37, no. 3, pp. 208–211, 2013. View at Publisher · View at Google Scholar · View at Scopus
  128. H. Yang, W. Xu, Z. Zhou et al., “Curcumin attenuates urinary excretion of albumin in type II diabetic patients with enhancing nuclear factor erythroid-derived 2-like 2 (Nrf2) system and repressing inflammatory signaling efficacies,” Experimental and Clinical Endocrinology & Diabetes : Official Journal, German Society of Endocrinology [and] German Diabetes Association, vol. 123, no. 6, pp. 360–367, 2015. View at Publisher · View at Google Scholar · View at Scopus
  129. E. H. Kobayashi, T. Suzuki, R. Funayama et al., “Nrf2 suppresses macrophage inflammatory response by blocking proinflammatory cytokine transcription,” Nature Communications, vol. 7, no. 5, p. 11624, 2016. View at Publisher · View at Google Scholar · View at Scopus
  130. P. Gao, L. Li, L. Ji et al., “Nrf2 ameliorates diabetic nephropathy progression by transcriptional repression of TGFbeta1 through interactions with c-Jun and SP1,” Biochimica et Biophysica Acta, vol. 1839, no. 11, pp. 1110–1120, 2014. View at Publisher · View at Google Scholar · View at Scopus
  131. C. Zoja, D. Corna, V. Nava et al., “Analogs of bardoxolone methyl worsen diabetic nephropathy in rats with additional adverse effects,” American Journal of Physiology Renal Physiology, vol. 304, no. 6, pp. F808–F819, 2013. View at Publisher · View at Google Scholar · View at Scopus
  132. N. D. Vaziri, S. Liu, S. H. Farzaneh, S. Nazertehrani, M. Khazaeli, and Y. Y. Zhao, “Dose-dependent deleterious and salutary actions of the Nrf2 inducer dh404 in chronic kidney disease,” Free Radical Biology & Medicine, vol. 86, no. 9, pp. 374–381, 2015. View at Publisher · View at Google Scholar · View at Scopus
  133. S. M. Tan, A. Sharma, N. Stefanovic et al., “Derivative of bardoxolone methyl, dh404, in an inverse dose-dependent manner lessens diabetes-associated atherosclerosis and improves diabetic kidney disease,” Diabetes, vol. 63, no. 9, pp. 3091–3103, 2014. View at Publisher · View at Google Scholar · View at Scopus
  134. S. Menegon, A. Columbano, and S. Giordano, “The dual roles of NRF2 in cancer,” Trends in Molecular Medicine, vol. 22, no. 7, pp. 578–593, 2016. View at Publisher · View at Google Scholar · View at Scopus
  135. J. Kim and Y. S. Keum, “NRF2, a key regulator of antioxidants with two faces towards cancer,” Oxidative Medicine and Cellular Longevity, vol. 2016, no. 6, p. 2746457, 2016. View at Publisher · View at Google Scholar · View at Scopus
  136. A. Ooi and K. A. Furge, “Fumarate hydratase inactivation in renal tumors: HIF1alpha, NRF2, and “cryptic targets” of transcription factors,” Chinese Journal of Cancer, vol. 31, no. 9, pp. 413–420, 2012. View at Publisher · View at Google Scholar · View at Scopus
  137. S. K. Niture and A. K. Jaiswal, “Nrf2-induced antiapoptotic Bcl-xL protein enhances cell survival and drug resistance,” Free Radical Biology & Medicine, vol. 57, no. 4, pp. 119–131, 2013. View at Publisher · View at Google Scholar · View at Scopus
  138. Y. Mitsuishi, K. Taguchi, Y. Kawatani et al., “Nrf2 redirects glucose and glutamine into anabolic pathways in metabolic reprogramming,” Cancer Cell, vol. 22, no. 1, pp. 66–79, 2012. View at Publisher · View at Google Scholar · View at Scopus
  139. S. Abdo, S. L. Zhang, and J. S. Chan, “Reactive oxygen species and nuclear factor erythroid 2-related factor 2 activation in diabetic nephropathy: a hidden target,” Journal of Diabetes & Metabolism, vol. 6, no. 6, 2015. View at Publisher · View at Google Scholar