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Cited 28 time in webofscience Cited 28 time in scopus
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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 injuryopen access

Authors
Lee, Jee EunKim, Jung EunLee, Mi HwaSong, Hye KyoungGhee, Jung YeonKang, Young SunMin, Hye SookKim, Hyun WookCha, Jin JooHan, Jee YoungHan, Sang YoubCha, Dae Ryong
Issue Date
May-2016
Publisher
NATURE PUBLISHING GROUP
Citation
LABORATORY INVESTIGATION, v.96, no.5, pp.547 - 560
Indexed
SCIE
SCOPUS
Journal Title
LABORATORY INVESTIGATION
Volume
96
Number
5
Start Page
547
End Page
560
URI
https://scholarworks.korea.ac.kr/kumedicine/handle/2020.sw.kumedicine/6480
DOI
10.1038/labinvest.2016.34
ISSN
0023-6837
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.
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Kang, Young Sun
Ansan Hospital (Department of Nephrology and Hypertension, Ansan Hospital)
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