Diabetic nephropathy (DN), a severe microvascular complication of diabetes mellitus (DM), results in high mortality due to the lack of effective interventions. The current study investigated the preventive effect of krill oil (KO) on DN using a type 2 DM mouse model induced by streptozotocin and high-fat diet for 24 weeks. The diabetic mice developed albuminuria, mesangial matrix accumulation, glomerular hypertrophy, and fibrosis formation, with an increase in renal proinflammatory, oxidative and profibrotic gene expression. KO significantly prevented these effects but did not improve hyperglycemia and glucose intolerance. In high-glucose-treated mesangial cells (MCs), KO preferably modulated TGF-β1 signaling as revealed by RNA-sequencing. In TGF-β1-treated MCs, KO abolished SMAD2/3 phosphorylation and nuclear translocation and activated Smad 7 gene expression. The action of KO on the SMADs was confirmed in the diabetic kidneys. Therefore, KO may prevent DN predominantly by suppressing the TGF-β1 signaling pathway.
Keyphrases
- diabetic nephropathy
- transforming growth factor
- gene expression
- epithelial mesenchymal transition
- high fat diet
- high glucose
- signaling pathway
- induced apoptosis
- mouse model
- dna methylation
- endothelial cells
- insulin resistance
- adipose tissue
- single cell
- fatty acid
- cardiovascular events
- physical activity
- skeletal muscle
- glycemic control
- endoplasmic reticulum stress
- pi k akt
- newly diagnosed
- oxidative stress
- cell death
- protein kinase
- blood glucose
- atomic force microscopy
- preterm birth