Vaccination against type 1 angiotensin receptor prevents streptozotocin-induced diabetic nephropathy.
Vaccination against type 1 angiotensin receptor prevents streptozotocin-induced diabetic nephropathy.
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1 型血管紧张素受体疫苗可预防链脲佐菌素诱发的糖尿病肾病
DOI：
10.1007/s00109-015-1343-6
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发表时间：
2016-02
期刊：
影响因子：
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通讯作者：
Chen X
中科院分区：
文献类型：
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作者：
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
近期，我们团队研发出一种针对血管紧张素（Ang）II 1型受体（AT1R）的治疗性高血压疫苗，名为ATRQβ - 001。为探究其对链脲佐菌素诱导的糖尿病肾病的潜在疗效，将雄性Sprague Dawley大鼠随机分为两组：对照组和糖尿病模型组。1周后，将糖尿病大鼠再分为四个亚组（每组15只），分别用生理盐水、奥美沙坦、ATRQβ - 001以及Qβ病毒样颗粒（VLP）进行为期14周的治疗。除降低血压外，ATRQβ - 001疫苗接种还通过抑制氧化应激、巨噬细胞浸润和促炎因子表达，改善了肾功能障碍的生化参数变化、肾小球系膜扩张及纤维化。此外，与奥美沙坦治疗相似，ATRQβ - 001疫苗接种抑制了肾脏血管紧张素II - AT1R的激活，并消除了血管紧张素转换酶2 - Ang（1 - 7）的下调，而仅在疫苗组未观察到循环或局部肾素 - 血管紧张素系统（RAS）明显的反馈激活。在大鼠肾小球系膜细胞中，抗ATR - 001抗体抑制了高糖诱导的转化生长因子 - β1（TGF） - β1/Smad3信号通路。另外，在接种疫苗的动物中未检测到明显的免疫介导损伤。总之，ATRQβ - 001疫苗通过调节两个RAS轴并抑制TGF - β1/Smad3信号通路，改善了链脲佐菌素诱导的糖尿病肾损伤，为治疗糖尿病肾病提供了一种新颖、安全且有前景的方法。
RAS的过度激活在糖尿病肾病（DN）的发展中起着关键作用。
我们的目的是验证ATRQβ - 001疫苗在链脲佐菌素诱导的DN中的有效性。
ATRQβ - 001调节了两个RAS轴并抑制了TGF - β1/Smad3信号通路。
疫苗疗法可能为治疗DN提供一种新颖、安全且有前景的方法。
本文的网络版本（doi:10.1007/s00109 - 015 - 1343 - 6）包含补充材料，仅供授权用户使用。
AbstractRecently, 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.Key messagesOveractivation 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.