We found a match
Your institution may have access to this item. Find your institution then sign in to continue.
- Title
PGC1α Activators Mitigate Diabetic Tubulopathy by Improving Mitochondrial Dynamics and Quality Control.
- Authors
Lee, So-Young; Kang, Jun Mo; Kim, Dong-Jin; Park, Seon Hwa; Jeong, Hye Yun; Lee, Yu Ho; Kim, Yang Gyun; Yang, Dong Ho; Lee, Sang Ho
- 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.
- Subjects
KIDNEY tubules; PEROXISOME proliferator-activated receptors; MITOCHONDRIAL pathology; AUTOPHAGY; MEDICAL quality control; HOMEOSTASIS; DISEASES
- Publication
Journal of Diabetes Research, 2017, p1
- ISSN
2314-6745
- Publication type
Article
- DOI
10.1155/2017/6483572