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DA-1229, a dipeptidyl peptidase IV inhibitor, protects against renal injury by preventing podocyte damage in an animal model of progressive renal injury

Authors
 Jee Eun Lee  ;  Jung Eun Kim  ;  Mi Hwa Lee  ;  Hye Kyoung Song  ;  Jung Yeon Ghee  ;  Young Sun Kang  ;  Hye Sook Min  ;  Hyun Wook Kim  ;  Jin Joo Cha  ;  Jee Young Han  ;  Sang Youb Han  ;  Dae Ryong Cha 
Citation
 LABORATORY INVESTIGATION, Vol.96(5) : 547-560, 2016 
Journal Title
 LABORATORY INVESTIGATION 
ISSN
 0023-6837 
Issue Date
2016
Abstract
Although dipeptidyl peptidase IV (DPPIV) inhibitors are known to have renoprotective effects, the mechanism underlying these effects has remained elusive. Here we investigated the effects of DA-1229, a novel DPPIV inhibitor, in two animal models of renal injury including db/db mice and the adriamycin nephropathy rodent model of chronic renal disease characterized by podocyte injury. For both models, DA-1229 was administered at 300?mg/kg/day. DPPIV activity in the kidney was significantly higher in diabetic mice compared with their nondiabetic controls. Although DA-1229 did not affect glycemic control or insulin resistance, DA-1229 did improve lipid profiles, albuminuria and renal fibrosis. Moreover, DA-1229 treatment resulted in decreased urinary excretion of nephrin, decreased circulating and kidney DPPIV activity, and decreased macrophage infiltration in the kidney. In adriamycin-treated mice, DPPIV activity in the kidney and urinary nephrin loss were both increased, whereas glucagon-like peptide-1 concentrations were unchanged. Moreover, DA-1229 treatment significantly improved proteinuria, renal fibrosis and inflammation associated with decreased urinary nephrin loss, and kidney DPP4 activity. In cultured podocytes, DA-1229 restored the high glucose/angiotensin II-induced increase of DPPIV activity and preserved the nephrin levels in podocytes. These findings suggest that activation of DPPIV in the kidney has a role in the progression of renal disease, and that DA-1229 may exert its renoprotective effects by preventing podocyte injury.
Files in This Item:
T201605697.pdf Download
DOI
10.1038/labinvest.2016.34
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실) > 1. Journal Papers
Yonsei Authors
Kim, Hyun Wook(김현욱) ORCID logo https://orcid.org/0000-0002-4274-7562
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/152932
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