Evogliptin, a Dipeptidyl Peptidase-4 Inhibitor, Attenuates Renal Fibrosis Caused by Unilateral Ureteral Obstruction in Mice.
Mi Jin KimNa Young KimYun A JungSeunghyeong LeeGwon Soo JungJung Guk KimIn Kyu LeeSungwoo LeeYeon Kyung ChoiKeun Gyu ParkPublished in: Diabetes & metabolism journal (2019)
Renal fibrosis is considered to be the final common outcome of chronic kidney disease. Dipeptidyl peptidase-4 (DPP-4) inhibitors have demonstrated protective effects against diabetic kidney disease. However, the anti-fibrotic effect of evogliptin, a DPP-4 inhibitor, has not been studied. Here, we report the beneficial effects of evogliptin on unilateral ureteral obstruction (UUO)-induced renal fibrosis in mice. Evogliptin attenuated UUO-induced renal atrophy and tubulointerstitial fibrosis. Immunohistochemistry and Western blotting demonstrated that evogliptin treatment inhibits pro-fibrotic gene expressions and extracellular matrix production. In vitro findings showed that the beneficial effects of evogliptin on renal fibrosis are mediated by inhibition of the transforming growth factor-β/Smad3 signaling pathway. The present study demonstrates that evogliptin is protective against UUO-induced renal fibrosis, suggesting that its clinical applications could extend to the treatment of kidney disease of non-diabetic origin.
Keyphrases
- transforming growth factor
- chronic kidney disease
- extracellular matrix
- high glucose
- epithelial mesenchymal transition
- signaling pathway
- type diabetes
- diabetic rats
- liver fibrosis
- oxidative stress
- systemic sclerosis
- endothelial cells
- cell proliferation
- adipose tissue
- copy number
- combination therapy
- wound healing
- peritoneal dialysis
- induced apoptosis