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

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

    Research output: Contribution to journalArticlepeer-review

    26 Citations (Scopus)

    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.

    Original languageEnglish
    Pages (from-to)547-560
    Number of pages14
    JournalLaboratory Investigation
    Volume96
    Issue number5
    DOIs
    Publication statusPublished - 2016 May 1

    ASJC Scopus subject areas

    • Pathology and Forensic Medicine
    • Molecular Biology
    • Cell Biology

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