Antifibrotic effects of KS370G, a caffeamide derivative, in renal ischemia-reperfusion injured mice and renal tubular epithelial cells
Journal
Scientific Reports
Journal Volume
4
Pages
5814
Date Issued
2014
Author(s)
Abstract
Accumulating evidence suggests that renal tubulointerstitial fibrosis is a main cause of end-stage renal disease. Clinically, there are no beneficial treatments that can effectively reverse the progressive loss of renal functions. Caffeic acid phenethyl ester is a natural phenolic antifibrotic agent, but rapid decomposition by an esterase leads to its low bioavailability. In this study, we evaluated the effects of KS370G, a caffeic acid phenylethyl amide, on murine renal fibrosis induced by unilateral renal ischemia-reperfusion injury (IRI) and in TGF-β1 stimulated renal tubular epithelial cells (NRK52E and HK-2). In the animal model, renal fibrosis was evaluated at 14 days post-operation. Immediately following the operation, KS370G (10 mg/kg) was administered by oral gavage once a day. Our results show that KS370G markedly attenuates collagen deposition and inhibits an IRI-induced increase of fibronectin, vimentin, α-SMA and TGF-β1 expression and plasma TGF-β1 levels in the mouse kidney. Furthermore, KS370G reverses TGF-β1-induced downregulation of E-cadherin and upregulation of a-SMA and also decreases the expression of fibronectin, collagen I and PAI-1 and inhibits TGF-β1-induced phosphorylation of Smad2/3. These findings show the beneficial effects of KS370G on renal fibrosis in vivo and in vitro with the possible mechanism being the inhibition of the Smad2/3 signaling pathway.
SDGs
Other Subjects
caffeic acid derivative; collagen; fibronectin; fizzy related protein; Fzr1 protein, mouse; KS370G; protease nexin I; Serpine2 protein, mouse; Smad2 protein; Smad2 protein, mouse; Smad3 protein; Smad3 protein, mouse; Tgfb1 protein, mouse; transforming growth factor beta1; vimentin; animal; cell line; drug effects; epithelial mesenchymal transition; epithelium cell; fibrosis; human; Institute for Cancer Research mouse; ischemia; Kidney Diseases; kidney tubule; male; metabolism; pathology; phosphorylation; physiology; protein processing; reperfusion injury; vascularization; Animals; Caffeic Acids; Cdh1 Proteins; Cell Line; Collagen; Epithelial Cells; Epithelial-Mesenchymal Transition; Fibronectins; Fibrosis; Humans; Ischemia; Kidney Diseases; Kidney Tubules; Male; Mice, Inbred ICR; Phosphorylation; Protein Processing, Post-Translational; Reperfusion Injury; Serpin E2; Smad2 Protein; Smad3 Protein; Transforming Growth Factor beta1; Vimentin
Type
journal article