Empagliflozin Ameliorates Kidney Injury in Diabetic Nephropathy via SIRT1 and TXNIP

SGLT2 inhibitor empagliflozin can slower the decline of eGFR and reduce the occurrence rate of end-stage kidney disease according to EMPA-REG OUTCOME Clinical Trail. However, the mechanism is still poorly understood. Sirtuin 1 (SIRT1) and Thioredoxin-interacting protein (TXNIP) are known to play important roles in metabolism-related disease, including diabetic nephroathy. To illustrate whether SIRT1 and TXNIP play roles in empagliflozin ameliorates high-fat diet induced kidney injury. In our study, the mouse mesangial cell SV40 MES 13 was cultured in 5.6 mmol/L glucose (NG)or 30mmol/L glucose(HG) with or without 50,250,500 or 1000nmol/L empagliflozin (HG+Empa-50; HG+Empa-250; HG+Empa-500;HG+Empa-1000) for 48 hours. Western Blot analysis showed that empaglifozin (500 nmol/L and 1000 nmol/L, respectively) could reverse the protein of Cleaved caspased3 expression induced by HG in SV40 MES 13 cells. In addition, empaglifozin significantly decreased TXNIP(50,250,500 and 1000 nmol/L, respectively) and increased SIRT1 protein levels(50,250,500 and 1000 nmol/L, respectively) in HG-induced SV40 MES 13 cells. Above all, when we treat cells with empaglifozin(500nmol/L and 1000nmol/L), the apoptosis was ameliorated and the expression of SIRT1,TXNIP was reversed that induced by HG. Collectively, the data indicates that the effect of empaglifozin on renoprotection is correlated with ameliorating the apoptosis in the kidney which may be via SIRT1 and TXNIP. Disclosure R. Liang: None. M. Wang: None. F. Xu: None. M. Cai: None.