PPARγ and PGC-1α activators protect against diabetic nephropathy by suppressing the inflammation and NF-κB activation

Background: Inflammation played critical roles in the progression of various kidney diseases and leaded to irreversible kidney fibrosis. Peroxisome proliferator-activated receptor gamma (PPARγ) and its coactivator PPARγ coactivator-1 alpha (PGC-1α) negatively regulated mitochondrial biogenesis, cellular energy metabolism, and inflammation. But the cooperative molecular mechanism of them in kidney remained unclear. The aim of present study was to investigate this issue. Methods: : Human proximal tubular HK-2 cell line was stimulated by inflammatory factors, and the expression of PPARγ and its coregulators were determined via reverse transcription-quantitative polymerase chain reaction and western blotting, and DNA binding capacity was measured by EMSA. Furthermore, db/db mice were used to establish a diabetic nephropathy model and administrated with PPARγ and PGC-1α activator. Kidney injury was evaluated microscopically, and inflammatory mechanism was assessed by western blotting. Results: : Our results revealed that either TNF-α or IL-1b could significantly decreased PPARγ and PGC-1 expression in vitro. Cytokines also obviously inhibited PPARγ DNA binding activities. Meanwhile, we detected rapid activation of NF-κB pathway under the same experimental conditions. PPARγ and PGC-1α activators effectively protect against diabetic nephropathy and suppress NF-κB expression in db/db mice. Conclusions: : PPARγ and its coactivator PGC-1α actively participated in the protection against renal inflammation through regulating NF-κB pathway, which highlighted a potential therapeutic target for renal diseases.