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Deprecated: Implicit conversion from float 231.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 J+Mol+Med+(Berl) 2016 ; 94 (2): 207-18 Nephropedia Template TP
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Vaccination against type 1 angiotensin receptor prevents streptozotocin-induced diabetic nephropathy #MMPMID26407577
Ding D; Du Y; Qiu Z; Yan S; Chen F; Wang M; Yang S; Zhou Y; Hu X; Deng Y; Wang S; Wang L; Zhang H; Wu H; Yu X; Zhou Z; Liao Y; Chen X
J Mol Med (Berl) 2016[]; 94 (2): 207-18 PMID26407577show ga
Abstract: Recently, our group has developed a therapeutic hypertensive vaccine against angiotensin (Ang) II type 1 receptor (AT1R) named ATRQ?-001. To explore its potential effectiveness on streptozotocin-induced diabetic nephropathy, male Sprague Dawley rats were randomly divided into two groups: a control and a diabetic model. After 1 week, the diabetic rats were divided into four subgroups (each with 15 rats) for 14-week treatments with saline, olmesartan, ATRQ?-001, and Q? virus-like particle (VLP), respectively. In addition to lower blood pressure, ATRQ?-001 vaccination ameliorated biochemical parameter changes of renal dysfunction, mesangial expansion, and fibrosis through inhibiting oxidative stress, macrophage infiltration, and proinflammatory factor expression. Furthermore, ATRQ?-001 vaccination suppressed renal Ang II-AT1R activation and abrogated the downregulation of angiotensin-converting enzyme 2-Ang (1?7), similar to olmesartan treatment, while no obvious feedback activation of circulating or local renin-angiotensin system (RAS) was only observed in vaccine group. In rat mesangial cells, the anti-ATR-001 antibody inhibited high glucose-induced transforming growth factor-?1 (TGF)-?1/Smad3 signal pathway. Additionally, no significant immune-mediated damage was detected in vaccinated animals. In conclusion, the ATRQ?-001 vaccine ameliorated streptozotocin-induced diabetic renal injury via modulating two RAS axes and inhibiting TGF-?1/Smad3 signal pathway, providing a novel, safe, and promising method to treat diabetic nephropathy. Key messages: Overactivation of RAS plays a crucial role in the development of the DN.Our aim was to verify the effectiveness of ATRQ?-001 vaccine in STZ-induced DN.The ATRQ?-001 modulated two RAS axes and inhibited TGF-?1/Smad3 signal pathway.The vaccine therapy may provide a novel, safe, and promising method to treat DN. Electronic supplementary material: The online version of this article (doi:10.1007/s00109-015-1343-6) contains supplementary material, which is available to authorized users.
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J+Mol+Med+(Berl) 2016 ; 94 (2): 207-18
