Krill Oil Turns Off TGF-β1 Profibrotic Signaling in the Prevention of Diabetic Nephropathy
Xuechun Sun, Yu Yang, Xiaodan Sun, Huali Meng, Wenhao Hao, Jialin Yin, Fuzhe Ma, Xin Guo, Lei Du, Lei Sun, Hao Wu
Abstract
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 Smad7 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.