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.
Our modified laparoscopic intra-abdominal fixation technique using suture passer hernia forceps is a simple and safe method for PD catheter placement and is effective in minimizing the risk of catheter migration.
Objective:
To identify the significance of autophagy in lupus nephritis (LN).
Methods:
The number of autophagosomes in podocytes was counted and the expression of multiple molecular markers associated with autophagy was evaluated in LN specimens: in renal biopsy specimens from 90 patients with LN and 15 healthy controls, autophagosomes in podocytes were counted using transmission electron microscopy and the expression levels of four autophage related proteins including Beclin-1, microtubule-associated protein light chain 3 (LC3), autophagy-related gene 7 (Atg7), and UNC-51-like kinase 1 (ULK1) were measured using immunohistochemistry.
Results:
The number of autophagosomes in patients with LN types III, IV, and combined V–IV type were significantly higher than in controls (
p
< 0.0001;
p
< 0.0001;
p
= 0.009, respectively). However, the autophagosomes numbers in patients with II and V types LN were significantly lower than controls (both
p
< 0.0001). Various levels of marker expression were identified, and they correlated significantly with LN pathology classifications. Moreover, the percentage of marker expression in LN types III, IV and V-IV were significantly higher than controls (
p
< 0.05), while that in types II and V were lower than controls, although the difference for LC3 and ULK1 was not statistically significant.
Conclusions:
Autophagy activity and expression pattern of autophagy-related markers in podocytes were significantly positively correlated with LN of types III, IV, and V–IV, but negatively correlated with II and V types. Therefore autophagy could be a useful predictor of LN pathology type, and be informative and helpful in the development of treatment strategies in clinical settings.
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