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

Abstract 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.