DNA aptamer raised against AGEs blocks the progression of experimental diabetic nephropathy.
DNA aptamer raised against AGEs blocks the progression of experimental diabetic nephropathy.
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DOI：
10.2337/db12-1608
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发表时间：
2013-09
期刊：
影响因子：
7.7
通讯作者：
Yamagishi S
中科院分区：
文献类型：
--
作者：
Kaida Y;Fukami K;Matsui T;Higashimoto Y;Nishino Y;Obara N;Nakayama Y;Ando R;Toyonaga M;Ueda S;Takeuchi M;Inoue H;Okuda S;Yamagishi S
晚期糖基化终产物(AGEs)及其受体(RAGE)在糖尿病肾病中起重要作用。我们在体外筛选了针对AGEs的DNA适配子(AGEs-适配子)，并研究了其对2型糖尿病动物模型KKAy/Ta小鼠肾脏损伤的影响。8周龄雄性KKAy/Ta或C57BL/6J小鼠接受连续8周的AGEs-或对照-适配子注射。检测到AGEs-适配子，肾脏中AGEs-适配子水平升高至少7天。AGEs-适配子在肾脏的消除半衰期约为7天。与C57BL/6J小鼠相比，KKAy/Ta小鼠肾小球AGEs水平显著升高，并被AGEs适体阻断。AGEs适体可使KKAy/Ta小鼠尿白蛋白和8-羟基-2‘-脱氧鸟苷水平升高，肾小球肥大和细胞外基质积聚增加。此外，AGEs适体显著降低了KKAy/Ta小鼠肾脏和暴露于AGE的人肾小球系膜细胞中RAGE、单核细胞趋化蛋白-1、结缔组织生长因子和IV型胶原的基因表达。我们目前的数据表明，持续给予AGEs适体可以通过阻断AGEs-RAGE轴来保护实验性糖尿病肾病，这可能是治疗糖尿病肾病的一种可行且有前景的治疗策略。
Advanced glycation end products (AGEs) and their receptor (RAGE) play a role in diabetic nephropathy. We screened DNA aptamer directed against AGEs (AGEs-aptamer) in vitro and examined its effects on renal injury in KKAy/Ta mice, an animal model of type 2 diabetes. Eight-week-old male KKAy/Ta or C57BL/6J mice received continuous intraperitoneal infusion of AGEs- or control-aptamer for 8 weeks. AGEs-aptamer was detected and its level was increased in the kidney for at least 7 days. The elimination half-lives of AGEs-aptamer in the kidney were about 7 days. Compared with those in C57BL/6J mice, glomerular AGEs levels were significantly increased in KKAy/Ta mice, which were blocked by AGEs-aptamer. Urinary albumin and 8-hydroxy-2′-deoxy-guanosine levels were increased, and glomerular hypertrophy and enhanced extracellular matrix accumulation were observed in KKAy/Ta mice, all of which were prevented by AGEs-aptamer. Moreover, AGEs-aptamer significantly reduced gene expression of RAGE, monocyte chemoattractant protein-1, connective tissue growth factor, and type IV collagen both in the kidney of KKAy/Ta mice and in AGE-exposed human cultured mesangial cells. Our present data suggest that continuous administration of AGEs-aptamer could protect against experimental diabetic nephropathy by blocking the AGEs-RAGE axis and may be a feasible and promising therapeutic strategy for the treatment of diabetic nephropathy.
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影响因子：
6.1
作者：
Inagaki, Y;Yamagishi, S;Makita, Z
通讯作者：
Makita, Z
影响因子：
2.9
作者：
King, DJ;Ventura, DA;Gorenstein, DG
通讯作者：
Gorenstein, DG
影响因子：
7.8
作者：
Osborne, SE;Matsumura, I;Ellington, AD
通讯作者：
Ellington, AD
影响因子：
13.6
作者：
Coughlan, Melinda T.;Thorburn, David R.;Forbes, Josephine M.
通讯作者：
Forbes, Josephine M.
DOI：
10.2174/187153007780832118
发表时间：
2007-06-01
影响因子：
1.9
作者：
Fukami, K.;Yamagishi, S.;Okuda, S.
通讯作者：
Okuda, S.