ks370g and Kidney-Diseases

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 α-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.

Topics: 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