Curcumin alleviates diabetic nephropathy via inhibiting podocyte mesenchymal transdifferentiation and inducing autophagy in rats and MPC5 cells

Abstract

Context: Curcumin could ameliorate diabetic nephropathy (DN), but the mechanism remains unclear.

Objective: The efficacy of curcumin on epithelial-to-mesenchymal transition (EMT) of podocyte and autophagy in vivo and in vitro was explored.

Materials and methods: Thirty male Sprague–Dawley rats were divided into the normal, model and curcumin (300 mg/kg/d, i.g., for 8 weeks) groups. Rats received streptozotocin (50 mg/kg, i.p.) and high-fat-sugar diet to induce DN. Biochemical indicators and histomorphology of renal tissues were observed. In addition, cultured mouse podocytes (MPC5) was induced to EMT with serum from DN rats, and then exposed to curcumin (40 µM) with or without fumonisin B1, an Akt specific activator or 3BDO, the mTOR inducer. Western blot analysed the levels of EMT and autophagy associated proteins.

Results: Administration of curcumin obviously reduced the levels of blood glucose, serum creatinine, urea nitrogen and urine albumen (by 28.4, 37.6, 33.5 and 22.4%, respectively), and attenuated renal histomorphological changes in DN rats. Podocytes were partially fused and autophagic vacuoles were increased in curcumin-treated rats. Furthermore, curcumin upregulated the expression of E-cadherin and LC3 proteins and downregulated the vimentin, TWIST1, p62, p-mTOR, p-Akt and P13K levels in DN rats and MPC5 cells. However, fumonisin B1 or 3BDO reversed the effects of curcumin on the expression of these proteins in cells.

Discussion and conclusions: The protection against development of DN by curcumin treatment involved changes in inducing autophagy and alleviating podocyte EMT, through the PI3k/Akt/mTOR pathway, providing the scientific basis for further research and clinical applications of curcumin.

Keywords:

• Glomerular podocytes
• epithelial-to-mesenchymal transition
• P13K/Akt
• mTOR

Disclosure statement

The authors declare that they have no conflicts of interest regarding the publication of this article.

Additional information

Funding

The work was financially supported by the Medicine and Medical Science and Technology Project of Zhejiang Province (No. 2018ZA016).