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Abstract: FR-PO345

SIRT3 Activation with Viniferin Treatment Ameliorates Features of Diabetes-Induced Tubular Injury Through Restoration of Mitochondrial Function

Session Information

Category: Diabetic Kidney Disease

  • 701 Diabetic Kidney Disease: Basic

Authors

  • Ryu, Jaejin, Department of Internal Medicine, College of Medicine, Yonsei University, Seoul, Korea (the Republic of)
  • Kim, Jae Young, Division of Nephrology, Department of Internal Medicine, National Health Insurance Service Ilsan Hospital, Goyang-si, Gyeonggi-do, Korea (the Republic of)
  • Nam, Boyoung, Department of Internal Medicine, College of Medicine, Yonsei University, Seoul, Korea (the Republic of)
  • Kim, Gyu Ri, Department of Internal Medicine, College of Medicine, Yonsei University, Seoul, Korea (the Republic of)
  • Ko, Ye Eun, Department of Internal Medicine, College of Medicine, Yonsei University, Seoul, Korea (the Republic of)
  • Kim, Hyung Woo, Department of Internal Medicine, College of Medicine, Yonsei University, Seoul, Korea (the Republic of)
  • Han, Seung Hyeok, Department of Internal Medicine, College of Medicine, Yonsei University, Seoul, Korea (the Republic of)
  • Yoo, Tae-Hyun, Department of Internal Medicine, College of Medicine, Yonsei University, Seoul, Korea (the Republic of)
  • Kang, Shin-Wook, Department of Internal Medicine, College of Medicine, Yonsei University, Seoul, Korea (the Republic of)
  • Park, Jung Tak, Department of Internal Medicine, College of Medicine, Yonsei University, Seoul, Korea (the Republic of)
Background

Oxidative stress and mitochondrial dysfunction are key factors inducing diabetic nephropathy. In this study, the role of SIRT3 as a regulator of mitochondrial activity and cell survival and the effect of viniferin as a SIRT3 activator were assessed in diabetes-induced tubular injury.

Methods

In vitro, NRK-52E cells treated with TGF-β-were compared with controls after SIRT3-targeted lentivirus transfection and viniferin treatment to evaluate the effect of SIRT3 overexpression. In an animal study, viniferin was injected to db/db mice for 9 weeks and to C57BL/6 mice given with unilateral nephrectomy and intraperitoneal streptozotocin injection (UNXSTZ) for 4 weeks using osmotic pump, db/m mice and C57BL/6 mice served as controls, respectively.

Results

In NRK-52E cells, TGF-β treatment resulted in decreased expression of SIRT3, in parallel with increased oxidative stress, decreased mitochondrial mass, integrity, and respiration, and increased fibrotic and apoptotic activities. SIRT3 overexpression by lentiviral transfection improved mitochondrial dynamics and cell injury, and similar alterations were observed after viniferin treatment. In kidney of db/db and UNXSTZ mice, diabetes induced downregulation of SIRT3, increased oxidative stress, decreased expressions of mitochondrial dynamic-related genes, and cell injury. SIRT3 activation by viniferin treatment restored these alterations, and tubular degeneration and fibrotic remodeling in diabetic kidney were also ameliorated by viniferin treatment.

Conclusion

This study demonstrates that SIRT3 activation by viniferin treatment improves oxidative stress and impaired mitochondrial metabolism in diabetes-induced tubular injury.