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Curcumin ameliorates epithelial-to-mesenchymal transition of podocytes in vivo and in vitro via regulating caveolin-1
Affiliation:1. Research Institute of Atherosclerotic Disease, Xi''an Jiaotong University Cardiovascular Research Center, Xi''an 710061, China;2. Laboratory Animal Center, Xi''an Jiaotong University Health Science Center, Xi''an 710061, China;3. Department of Pharmacology, Xi''an Jiaotong University Health Science Center, Xi''an 710061, China;4. Department of Pharmacy, Yangquan Coalmine Group General Hospital, Yangquan 045000, China;5. Department of Pharmacy, the First Affiliated Hospital of Xi''an Medical College, Xi''an 710061, China;6. School of Pharmacy, Xi''an Jiaotong University Health Science Center, Xi''an 710061, China
Abstract:AimsEpithelial-mesenchymal transition (EMT) is recognized to play a key role in diabetic nephropathy (DN). Curcumin, the main active component of turmeric extracted from the roots of the Curcuma longa plant, has been reported for its anti-fibrotic effects in kidney fibrosis. The purpose of our study was to investigate the effects of curcumin in reversing epithelial-to-mesenchymal transition (EMT) of podocytes in vivo and in vitro.Materials/methodsIn vivo streptozotocin (STZ)-induced diabetic rats received vehicle or curcumin, and podocytes were treated with high glucose (HG) in the presence or absence of curcumin in vitro. And we investigated the effect of curcumin on HG-induced phosphorylation of cav-1 on the stability cav-1 and β-catenin using immunoprecipitation and fluorescence microscopy analysis.ResultsCurcumin treatment dramatically ameliorated metabolic parameters, renal function, morphological parameters in diabetic rats. We found that HG treatment led to significant down-regulation of p-cadherin and synaptopodin, as well as remarkable up-regulation of α-SMA and FSP-1 in vivo and in vitro. Furthermore, curcumin inhibited HG-induced caveolin-1 (cav-1) Tyr14 phosphorylation associating with the suppression of stabilization of cav-1 and β-catenin.ConclusionsIn summary, these findings suggest that curcumin prevents EMT of podocytes, proteinuria, and kidney injury in DN by suppressing the phosphorylation of cav-1, and increasing stabilization of cav-1 and β-catenin.
Keywords:Epithelial-to-mesenchymal transition  Diabetic nephropathy  Caveolin-1  β-catenin
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