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논문분류	춘계학술대회 초록집
제목	Dipeptidyl peptidase-4 inhibition protects against renal injury through protection of podocyte injury
저자	Dae-Ha Kim* 1, Gyu Sik Choi1, Jin Joo Cha, Hye Sook Min 1, Ji Eun Lee2, Hyun Wook Kim2, Jung Yeon Ghee1, Ji Ae Yoo1, Ki Tae Kim1, Sang Youb Han3, Kum Hyun Han3, Se Won Oh3, Dae Ryong Cha1, Jee Young Han4, Young Sun Kang1
출판정보	2016; 2016(1):
키워드	Adriamycin induced nephropathy, DPP-4 inhibitor , podocyte
초록	Background: Many experimental and clinical trials suggest that DPP-4 inhibition decrease albuminuria in diabetic nephropathy (DN) and provided the potential to delay the onset and progression of DN independent of glycemic controls. Taken together these findings suggest the possibility that DPP-4 inhibition may have effects on podocyte function in DN. Therefore, we investigated the effects of DPP-4 inhibition on podocyte function. Methods: We investigated the effects of DPP-4 inhibitor, in two animal models of podocyte injury including db/db mice and the adriamycin nephropathy (ADX). DPP-4 inhibitor was administered for 3months in db/db mice and for 3weeks in ADX model, and examined the effects of DPP-4 inhibitor on podocyte injury. Additionally, we performed in vitro experiments using podocyte to further define the molecular mechanism of DPP-4 inhibitor in podocyte injury. Results: For both models, DPPIV activity in the kidney was significantly higher in diabetic mice and ADX mice compared with controls. DPP-4 inhibition resulted in significant decrease in urinary albumin excretion, and urinary excretion of nephrin, decreased DPP-4 activity in the kidney. In ADX mice, similar renoprotective effects were observed, while GLP-1 concentrations were unchanged. In both models, DPP-4 inhibitor treatment revealed that glomerular nephrin expression was significantly restored, and numbers of WT-1 positive-stained cells in the glomeruli were significantly increased compared to that in controls. In cultured podocytes, DPP-4 inhibitor restored the high glucose/angiotensin II-induced increase of DPP-4 activity and preserved the nephrin levels in podocytes. In addition, we also observed that DPP-4 inhibitor treatment significantly increased podocyte survival from high glucose-induced cytotoxic injury using MTT assay. Interestingly, stimulation with high glucose and angiotensin II markedly reduced the cellular level of nephrin, while treatment with DPP-4 inhibitor effectively restored nephrin production. Conclusion: These findings suggest that activation of DPP-4 in the kidney plays a role in the progression of renal disease, and DPP-4 inhibition may protect against renal injury possibly mediated by improvement of podocyte injury. Targeted therapy inhibiting DPP-4 may prove to be a useful new approach in the management of progressive renal disease, independent of mechanisms mediated by glucagon-like peptide-1.
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