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논문분류	춘계학술대회 초록집
제목	Gemigliptin attenuates adriamycin induced nephropathy
저자	Da Rae Kim*, Shin Yeong Lee, Jin Sug Kim, Sang Ho Lee, Yang Gyun Kim, Kyung-Hwan Jeong, Ju Young Moon, Tae Won Lee, Chun Gyoo Ihm, Su Woong Jung, Yu Ho Lee, Da Wun Jeong , Ki-Pyo Kim
출판정보	2016; 2016(1):
키워드	Adriamycin induced nephropathy, Apoptosis, Gemigliptin, Podocyte injury
초록	Background: Previous studies demonstrated anti-apoptotic and anti-inflammatory potential of dipeptidyl peptidase-4[DPP-IV] in renal injury experiments. In our study, we assumed that renoprotective effect of gemigliptin in adriamycin induced nephropathy might be mediated by suppression of apoptosis, inflammation and oxidative stress. Methods: Using a murine model of adriamycin induced nephropathy, we established four treatment groups which received a single intravenous injection of normal saline, gemigliptin, adriamycin and gemigliptin plus adriamycin into the tail vein. At day 30 after intravenous injection, body weight change, urine albumin creatinine ratio[UACR] and serum glucose levels were compared between the four groups. Apoptosis, inflammation and oxidative stress-related molecules were analyzed by western blot analysis and real time PCR. Glomerulosclerotic index[GSI] and tubulointerstitial index[TII] were evaluated under light microscopy. As the markers of podocyte injury, WT-1 and nephrin score were also evaluated by immunofluorescence examination. Results: Body weight of adriamycin group was significantly decreased compared with control group. Urine albumin creatinine ratio(UACR) of day 15 were significantly reduced in adriamycin plus gemigliptin group compared with adriamycin group.(mg/g, 162.5±104.57 vs 223.9±100.56, p=0.049). Serum glucose levels were no significant difference between the four groups(p=0.509). Serum DPP-IV activity and active GLP-1 level were significantly decreased in the gemigliptin treatment group compared to that in adriamycin group. But renal DPP-IV activity and renal GLP-1R level did not show statistically significant differences between adriamycin and gemigliptin treatment. GSI and TII were significantly increased in adriamycin group but they are restored in gemigliptin plus adriamycin treatment.(GSI: 62.79% vs. 21.93%, p=0.005, TII: 16.29% vs. 3.74%, p=0.012) As the markers of apoptosis, inflammation and oxidative stress, Nitrotyrosine, iNOS, Bax/Bcl-2 ratio, NOX4, MCP-1, PAI-1, TNF-a and TGF-B1 levels were increased in adriamycin group whereas adriamycin plus gemigliptin treatment decreased this effect. WT-1 and nephrin score showed significantly restored in adriamycin plus gemigliptin group compared with adriamycin group (WT-1:15.60 vs. 8.267, p=0.0001, Nephrin score: 3.537 vs. 2.092, p=0.04). Conclusion: Our study showed that treatment of gemigliptin leads to a decrease of inflammation, apoptosis and oxidative stress in the mice model of adriamycin induced nephropathy. But, further experimental and clinical studies are needed to elucidate the pathogenesis.
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