511-P: The Renoprotective Effect of Evogliptin, a Dipeptidyl Peptidase-4 Inhibitor, in a Mouse Model of Renal Fibrosis

Abstract

Background: Renal tubulointerstitial fibrosis is a major pathologic finding of nearly all cause of end-stage renal disease. Dipeptidyl peptidase-4 (DPP-4) inhibitors are widely used in the treatment of patients with type 2 diabetes and have proven protective effects on diabetic kidney disease. This study aimed to investigate possible beneficial effects of evogliptin on renal fibrosis in mice. Methods: We examined the effects of evogliptin on renal tubulointerstitial fibrosis following unilateral ureteral obstruction (UUO) in mice. We further defined the role of evogliptin on transforming growth factor-β (TGF-β)/Smad signaling pathways in renal tubulointerstitial fibrosis through in vivo and in vitro study. Results: Through hematoxylin/eosin and sirius red staining, we observed that evogliptin effectively ameliorates UUO-induced renal atrophy and fibrosis. Immunohistochemistry in conjunction with western blot analysis revealed that evogliptin treatment inhibited UUO-induced up-regulation of phosphorylated Smad3, α-smooth muscle actin, plasminogen activator inhibitor 1, fibronenctin, and type 1 collagen. In vitro experiments with proximal tubule epithelial cell suggested that the effects of evogliptin on UUO-induced renal fibrosis are mediated by inhibition of the TGF-β/Smad signaling pathway. Conclusion: The present study demonstrates that evogliptin has a protective effect on UUO-induced renal tubulointerstitial fibrosis, suggesting that its clinical applications could extend to the treatment of nondiabetic origin renal disease. Disclosure N. Kim: None. I. Lee: Board Member; Self; NovMetapharm Co, Inc. S. Park: None. M. Kim: None. J. Kim: None. Y. Choi: None. K. Park: None. M. Kim: None. Funding National Research Foundation of Korea