Seabuckthorn polysaccharide alleviates renal fibrosis in a mouse model of diabetic nephropathy via p311/TGFβ1/Fstl1 signaling pathway.

Background: Diabetic nephropathy (DN) is a primary microvascular complication of diabetes with characteristics of renal fibrosis. Seabuckthorn polysaccharide (SP) is an extract from Seabuckthron berries (Hippophae rhamnoides L.) with antioxidant, anti-fatigue, anti-inflammation, and hepatoprotective properties. This current work aimed to investigate the effect of SP on DN-induced kidney fibrosis.

Methods: STZ-induced DN mouse model was constructed by intraperitoneally injecting 50 mg/kg STZ for five days. Various doses of SP were orally administered to mice. Biochemical analysis was performed to measure blood biochemical parameters. Masson's trichrome staining of renal tissues was conducted to analyze fibrotic area. Immunofluorescence staining was performed to assess E-cadherin and α-SMA expressions in kidney samples. Serum MMP2 level was evaluated by corresponding ELISA kit, and Timp2 level was subjected to RT-qPCR analysis. PCR and western blot were conducted to quantify p311, TGFβ1, and Fstl1 levels in renal samples.

Results: SP reversed the changes in body weight, fasting blood glucose and renal function indicators in diabetic mice. SP lessened renal fibrotic areas in diabetic mice and inhibited epithelial-mesenchymal transition (EMT) by increasing E-cadherin level and reducing α-SMA expression. Fibrotic genes MMP2 and TIMP2 were highly expressed in mice with DN, and their dysregulated expressions were reversed by SP administration. Additionally, SP suppressed the activation of p311/TGFβ1/Fstl1 signaling pathway in renal tissues of diabetic mice.

Conclusions: SP alleviates diabetic nephropathy by improving renal functions, alleviating renal fibrosis, and hampering EMT process via downregulation of fibrotic genes and inactivation of the p311/TGFβ1/Fstl1 pathway.