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Journal of Diabetes Research
Volume 2017, Article ID 6483572, 15 pages
https://doi.org/10.1155/2017/6483572
Research Article

PGC1α Activators Mitigate Diabetic Tubulopathy by Improving Mitochondrial Dynamics and Quality Control

1Division of Nephrology, Department of Internal Medicine, CHA Bundang Medical Center, CHA University, Seongnam, Republic of Korea
2Division of Nephrology, Department of Internal Medicine, Kyung Hee University Hospital at Gangdong, Kyung Hee University, Seoul, Republic of Korea

Correspondence should be addressed to Dong Ho Yang; rk.ca.ahc@gnayhd and Sang Ho Lee; rk.ca.uhk@yendikhsl

Received 19 October 2016; Accepted 30 November 2016; Published 20 March 2017

Academic Editor: Jochen Reiser

Copyright © 2017 So-Young Lee 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.

Abstract

Purpose. In this study, we investigated the effect of PGC1α activators on mitochondrial fusion, fission, and autophagic quality control in renal tubular cells in a diabetic environment in vivo and in vitro. We also examined whether the upregulation of PGC1α attenuates diabetic tubulopathy by normalizing mitochondrial homeostasis. Methods. HKC8 cells were subjected to high-glucose conditions (30 mM D-glucose). Diabetes was induced with streptozotocin (STZ, 50 mg/kg i.p. for 5 days) in male C57/BL6J mice. AICAR or metformin was used as a PGC1α activator. Results. Treatment with the PGC1α activators AICAR and metformin improved functional mitochondrial mass in HKC8 cells in high-glucose conditions. Moreover, in renal proximal tubular cells, increased PGC1α activity correlated with the reversal of changes in Drp1, Mfn1, and LC3-II protein expression in a high-glucose environment. Normalized mitochondrial life cycles resulted in low ROS production and reduced apoptosis. AICAR and metformin treatment effectively mitigated albuminuria and renal histopathology and decreased the expression of TGFβ1 and αSMA in the kidneys of diabetic mice. Conclusions. Our results demonstrate that increases in PGC1α activity improve diabetic tubulopathy by modulating mitochondrial dynamics and autophagy.