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| Content Provider | Springer Nature Link |
|---|---|
| Author | Ding, Dan Du, Yimei Qiu, Zhihua Yan, Sen Chen, Fen Wang, Min Yang, Shijun Zhou, Yanzhao Hu, Xiajun Deng, Yihuan Wang, Shijia Wang, Liangping Zhang, Hongrong Wu, Hailang Yu, Xian Zhou, Zihua Liao, Yuhua Chen, Xiao |
| Copyright Year | 2015 |
| Abstract | Recently, our group has developed a therapeutic hypertensive vaccine against angiotensin (Ang) II type 1 receptor (AT1R) named ATRQβ-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, ATRQβ-001, and Qβ virus-like particle (VLP), respectively. In addition to lower blood pressure, ATRQβ-001 vaccination ameliorated biochemical parameter changes of renal dysfunction, mesangial expansion, and fibrosis through inhibiting oxidative stress, macrophage infiltration, and proinflammatory factor expression. Furthermore, ATRQβ-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-β1 (TGF)-β1/Smad3 signal pathway. Additionally, no significant immune-mediated damage was detected in vaccinated animals. In conclusion, the ATRQβ-001 vaccine ameliorated streptozotocin-induced diabetic renal injury via modulating two RAS axes and inhibiting TGF-β1/Smad3 signal pathway, providing a novel, safe, and promising method to treat diabetic nephropathy. Overactivation of RAS plays a crucial role in the development of the DN. Our aim was to verify the effectiveness of ATRQβ-001 vaccine in STZ-induced DN. The ATRQβ-001 modulated two RAS axes and inhibited TGF-β1/Smad3 signal pathway. The vaccine therapy may provide a novel, safe, and promising method to treat DN. |
| Starting Page | 207 |
| Ending Page | 218 |
| Page Count | 12 |
| File Format | |
| ISSN | 09462716 |
| Journal | Journal of Molecular Medicine |
| Volume Number | 94 |
| Issue Number | 2 |
| e-ISSN | 14321440 |
| Language | English |
| Publisher | Springer Berlin Heidelberg |
| Publisher Date | 2015-09-26 |
| Publisher Place | Berlin/Heidelberg |
| Access Restriction | One Nation One Subscription (ONOS) |
| Subject Keyword | Angiotensin receptor Streptozotocin Renin-angiotensin system Diabetic nephropathy Vaccine Molecular Medicine Human Genetics Internal Medicine |
| Content Type | Text |
| Resource Type | Article |
| Subject | Drug Discovery Molecular Medicine Genetics (clinical) |
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