Amelioration of diabetic kidney injury with dapagliflozin is associated with suppressing renal HMGB1 expression and restoring autophagy in obese mice

Abstract

Diabetic kidney disease (DKD) is a major cause of chronic and end-stage renal disease in diabetic patients. Here, we investigated protective effects and possible mechanisms of dapagliflozin on renal injury in diabetic mice. DKD mice were established by high fat diet (HFD) feeding. Half of DKD mice were randomly assigned to receive dapagliflozin treatment (200 μg/day) for 8 weeks. Renal lipid droplets, fibrosis, oxidative and endoplasmic reticulum stress were evaluated. Glomerular injury was assessed by immunohistochemistry and transmission electron microscopy. Dapagliflozin led to marked inhibition of ROS levels and endoplasmic reticulum stress in diabetic mice. HFD-induced loss of Podocin and Nephrin, and impaired podocytes were also improved with the treatment. Importantly, overexpression of HMGB1 and suppressed autophagy in the kidney were partly reversed by dapagliflozin. Therefore, we speculate that protective effects of dapagliflozin on DKD may be associated with suppression of HMGB1 expression and restoration of autophagy in the kidney.