Diabetic nephropathy (DN) is one of the major microvascular complications of diabetes, and mitochondrial dysfunction has been observed in the kidneys of diabetic patients. Tilapia skin peptides (TSPs) are mixtures of small-molecular-weight peptides derived from tilapia skin. Rising evidence suggests that bioactive peptides from marine sources are beneficial for DN. This study aimed to investigate whether TSPs can alleviate the pathological progress in experimental DN by improving mitochondrial dysfunction through the activation of Bnip3/Nix signaling. In the current study, TSPs treatment alleviated the metabolic parameters and renal morphology in streptozotocin-induced diabetic rats. Additionally, TSPs treatment significantly activated Bnip3/Nix signaling and improved the mitochondrial morphology, reversed the over-production of mitochondrial superoxide and cellular reactive oxygen species and the decreased mitochondrial membrane potential, thereby inhibiting the expressions of fibronectin, collagen IV and intercellular cell adhesion molecule-1 in glomerular mesangial cells induced by high glucose. Collectively, our results suggest that TSPs show the renoprotective effect on DN by improving mitochondrial dysfunction, and they can be a potential therapeutic strategy for DN.
Keywords: Bnip3/Nix signaling; diabetic nephropathy; fish peptides; lipid metabolism; mitochondria; renal fibrosis.