Abstract: Objective To study the effects of curcumine on renal tubular epithelial-mesenchymal transition (EMT) and its possible mechanisms. Methods The effect of curcumin on the morphology of human kidney cells (HKCs) in the presence of TGF-β1 alone or in combination with different concentration curcumine was observed by phase contrast microscopy. The expressions of E-cardhrin, keratin, vimentin, alpha smooth muscle actin (α-SMA),fibroblast-specific protein 1 (FSP1) and key proteins of AKT/mTOR pathway were analyzed by immunohistochemical stain and Western blot. Results HKC cells showed a classic cobblestone morphology. Exposure of HKCs to TGF-β1 for 72 h induced a complete conversion of the epithelial cell to myofibroblast. When HKCs were co-incubated with TGF-β1 and various concentrations of curcumin for 72 h, curcumine maintained the epithelial morphology in a dose-dependent manner (from 12.5 to 50 μg/mL), antagonizing TGF-β1-induced the down-regulation expression of E-cardhrin, keratin and the up-rgulation of FSP1, vimentin and α-SMA. Importantly. Curcumine effectively suppressed the activity of the Akt/mTOR pathway in HKCs as demonstrated by a remarkable reduction of the Akt, mTOR, p70S6K, 4E-BP1和eIF4E phosphorylation. Conclusions Curcumine is a potent inhibitor of TGF-β1-induced epithelial-mesenchymal transition (EMT) and antagonizes TGF-β1-driven fibrogenesis through inhibition of the activity of the Akt/mTOR pathway.

Key words: curcumine, renal fibrosis, epithelialto-mesenchymal transition (EMT), TGF-β1, AKt/mTOR pathway