Tilapia Skin Peptides Ameliorate Diabetic Nephropathy in STZ-Induced Diabetic Rats and HG-Induced GMCs by Improving Mitochondrial Dysfunction

Abstract

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.

Bioinformatics analysis of differentially expressed genes in diabetic foot ulcer and preliminary experimental verification

“…In 2016, approximately 18.6 million people were suffering from DFU worldwide, which seriously affects the life quality and expectancy of patients and is also a major public health problem with a heavy societal burden ( 7 ). In previous studies, it was observed that some genes were differentially expressed in DFU and control groups, which played different roles in the occurrence and development of diseases through different mechanisms of action ( 8 - 13 ). For example, rs1024611 polymorphism of the monocyte chemoattractant protein-1 ( MCP-1 ) gene is significantly correlated with MCP-1 expression and individual susceptibility to DFU ( 8 ).…”

Mitophagy in Diabetic Kidney Disease

“…Stimulation of mTOR/PINK1/Parkin-mediated mitophagy can improve renal inflammation, glomerular membrane dilatation, and extracellular matrix deposition (Wen et al, 2020). Stimulation of BNIP3/Nix signal transduction also has the same intervention effect (Jin et al, 2020).…”

Fucoxanthin ameliorated myocardial fibrosis in STZ-induced diabetic rats and cell hypertrophy in HG-induced H9c2 cells by alleviating oxidative stress and restoring mitophagy

“…58 In HG-induced glomerular mesangial cells, tilapia skin peptides improved mitochondrial dysfunction by upregulating Bnip3 and Nix expression and removing damaged mitochondria. 59 Importantly, Bnip3 specifically promotes the degradation of proteins in the electron transport chain without activating apoptosis, and the apoptosis-promoting effect of Bnip3 occurs when cells are severely damaged. 60 Therefore, we speculate that the downregulation of Bnip3 and Nix may cause damaged mitochondrial accumulation, leading to cardiomyocyte hypertrophy.…”