Green tea peptides ameliorate diabetic nephropathy by inhibiting the TGF-β/Smad signaling pathway in mice
Xuhui Chen, Lingli Sun, Dongli Li, Xingfei Lai, Shuai Wen, Ruohong Chen, Zhenbiao Zhang, Qiuhua Li, Shili Sun
Abstract
Diabetic nephropathy (DN) is the most important cause of middle and late-stage chronic kidney disease. Green tea polypeptides are extracted from tea pomace, and exhibit various pharmacological effects. In this study, we analyzed the reno-protective effects of green tea peptides in diabetic db/db mice, and explored the underlying mechanisms. Peptide treatment for 5 weeks significantly reduced the blood glucose levels and other indices of diabetes, and alleviated renal injury measured in terms of blood creatinine, urea nitrogen and urinary albumin/urinary creatinine levels. Mechanistically, the green tea peptides downregulated p-Smad2/3, α-SMA, ZO-1 and vimentin proteins in the kidney tissues, and elevated Smad7. Thus, green tea peptides inhibited the deposition of ECM proteins by suppressing excessive activation of the TGF-β/Smad signaling pathway and reducing fibronectin levels. On the other hand, tea peptides ameliorated renal injury by inhibiting the production of inflammatory factors (iNOS and TNF-α) by suppressing the NF-κB signaling pathway. In addition, we confirmed the inhibitory effect of green tea peptides on the TGF-β/Smad signaling pathway in TGF-β1-stimulated HK-2 cells. Therefore, tea peptides can be considered as an effective candidate for alleviating DN.