[HTML][HTML] Protective role of PGC-1α in diabetic nephropathy is associated with the inhibition of ROS through mitochondrial dynamic remodeling

K Guo, J Lu, Y Huang, M Wu, L Zhang, H Yu, M Zhang… - PLoS …, 2015 - journals.plos.org
K Guo, J Lu, Y Huang, M Wu, L Zhang, H Yu, M Zhang, Y Bao, JC He, H Chen, W Jia
PLoS One, 2015journals.plos.org
The overproduction of mitochondrial reactive oxygen species (ROS) plays a key role in the
pathogenesis of diabetic nephropathy (DN). However, the underlying molecular mechanism
remains unclear. Our aim was to investigate the role of PGC-1α in the pathogenesis of DN.
Rat glomerular mesangial cells (RMCs) were incubated in normal or high glucose medium
with or without the PGC-1α-overexpressing plasmid (pcDNA3-PGC-1α) for 48 h. In the
diabetic rats, decreased PGC-1α expression was associated with increased mitochondrial …
The overproduction of mitochondrial reactive oxygen species (ROS) plays a key role in the pathogenesis of diabetic nephropathy (DN). However, the underlying molecular mechanism remains unclear. Our aim was to investigate the role of PGC-1α in the pathogenesis of DN. Rat glomerular mesangial cells (RMCs) were incubated in normal or high glucose medium with or without the PGC-1α-overexpressing plasmid (pcDNA3-PGC-1α) for 48 h. In the diabetic rats, decreased PGC-1α expression was associated with increased mitochondrial ROS generation in the renal cortex, increased proteinuria, glomerular hypertrophy, and higher glomerular 8-OHdG (a biomarker for oxidative stress). In vitro, hyperglycemia induced the downregulation of PGC-1α, which led to increased DRP1 expression, increased mitochondrial fragmentation and damaged network structure. This was associated with an increase in ROS generation and mesangial cell hypertrophy. These pathological changes were reversed in vitro by the transfection of pcDNA3-PGC-1α. These data suggest that PGC-1α may protect DN via the inhibition of DRP1-mediated mitochondrial dynamic remodeling and ROS production. These findings may assist the development of novel therapeutic strategies for patients with DN.
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