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.

Yishen capsule promotes podocyte autophagy through regulating SIRT1/NF-κB signaling pathway to improve diabetic nephropathy

“…Increased formation of autophagosomes observed in vitro also confirmed autophagic disorder in this study. These findings are consistent with those reported by previous studies [ 21 , 22 ]. Resveratrol and genistein intervention increase the expression of LC3-II, reduce the expression of p62, activate autophagy, and promote podocyte repair in vitro [ 23 , 24 ].…”

Icariin Prevents Extracellular Matrix Accumulation and Ameliorates Experimental Diabetic Kidney Disease by Inhibiting Oxidative Stress via GPER Mediated p62-Dependent Keap1 Degradation and Nrf2 Activation

“…Impaired autophagy activity contributes to the pathogenesis of DN, and the recovery of autophagy activity may be a promising therapeutic target for DN. Currently, the latest studies have confirmed that the inhibition of PI3K/Akt/mTOR signaling pathway restored autophagy and ameliorate DN (Tu et al, 2019 ; Wang et al, 2019 ). Result showed that the phosphorylation levels of PI3K, Akt, and mTOR in diabetic rats and mesangial cells induced by high glucose were obviously decreased by icariin treatment.…”

Interleukin 37 (IL-37) Reduces High Glucose-Induced Inflammation, Oxidative Stress, and Apoptosis of Podocytes by Inhibiting the STAT3–Cyclophilin A (CypA) Signaling Pathway

“…The most common clinical feature of DN is progressive proteinuria due to impairment of the GFB, and the normal morphology and function of podocytes play an important role in proteinuria formation and maintenance of renal function [ 14 , 15 ]. In many studies, podocytes have been treated with high glucose to cause DN in experimental models [ 16 , 17 ]. In this study, we treated podocytes with high glucose to construct a cell model of DN, and found that high glucose induced increased levels of inflammation and cell damage in podocytes.…”