Diabetes Metab J.  2020 Feb;44(1):186-192. 10.4093/dmj.2018.0271.

Evogliptin, a Dipeptidyl Peptidase-4 Inhibitor, Attenuates Renal Fibrosis Caused by Unilateral Ureteral Obstruction in Mice

Affiliations
  • 1Division of Endocrinology and Metabolism, Department of Internal Medicine, School of Medicine, Kyungpook National University, Daegu, Korea. kpark@knu.ac.kr, exc4932@hanmail.net
  • 2Department of Biomedical Science, Graduate School, Kyungpook National University, Daegu, Korea.
  • 3BK21 Plus KNU Biomedical Convergence Program, Kyungpook National University, Daegu, Korea.
  • 4New Drug Development Center, Daegu-Gyeongbuk Medical Innovation Foundation, Daegu, Korea.

Abstract

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.

Keyword

Dipeptidyl-peptidase IV inhibitors; Kidney failure, chronic; Transforming growth factor beta

MeSH Terms

Animals
Atrophy
Blotting, Western
Diabetic Nephropathies
Dipeptidyl-Peptidase IV Inhibitors
Extracellular Matrix
Fibrosis*
Gene Expression
Immunohistochemistry
In Vitro Techniques
Kidney Diseases
Kidney Failure, Chronic
Mice*
Renal Insufficiency, Chronic
Transforming Growth Factor beta
Ureter*
Ureteral Obstruction*
Dipeptidyl-Peptidase IV Inhibitors
Transforming Growth Factor beta
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