Vaccination against type 1 angiotensin receptor prevents streptozotocin-induced diabetic nephropathy

• DOI: 10.1007/s00109-015-1343-6
• Publication Date: 2015-09-25T23:57:13Z
• Authors: Dan Ding; Yimei Du; Zhihua Qiu; Sen Yan; Fen Chen; Min Wang; Shijun Yang; Yanzhao Zhou; Xiajun Hu; Yihuan Deng; Shijia Wang; Liangping Wang; Hongrong Zhang; Hailang Wu; Xian Yu; Zihua Zhou; Yuhua Liao; Xiao Chen
• Keywords: Male; Blood Pressure; Kidney Function Tests; Receptor, Angiotensin, Type 1; Streptozocin; Diabetes Mellitus, Experimental; Transforming Growth Factor beta1; 03 medical and health sciences; 0302 clinical medicine; Drug Discovery; Renin; Animals; Genetics(clinical); Diabetic Nephropathies; Smad3 Protein; Medicine(all); Podocytes; Angiotensin II; Fibrosis; Peptide Fragments; Rats; 3. Good health; Disease Models, Animal; Molecular Medicine; Original Article; Biomarkers; Blood Chemical Analysis; Signal Transduction

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: control and model. After week, the four subgroups (each with 15 rats) for 14-week treatments saline, olmesartan, ATRQβ-001, Qβ virus-like particle (VLP), respectively. In addition to lower blood pressure, ATRQβ-001 vaccination ameliorated biochemical parameter changes of renal dysfunction, mesangial expansion, fibrosis through inhibiting oxidative stress, macrophage infiltration, proinflammatory factor expression. Furthermore, suppressed Ang II-AT1R activation abrogated downregulation angiotensin-converting enzyme 2-Ang (1-7), similar olmesartan treatment, while no obvious feedback circulating or local renin-angiotensin system (RAS) was only observed in group. rat cells, anti-ATR-001 antibody inhibited high glucose-induced transforming growth factor-β1 (TGF)-β1/Smad3 signal pathway. Additionally, significant immune-mediated damage detected vaccinated animals. conclusion, injury via modulating RAS axes TGF-β1/Smad3 pathway, providing novel, safe, promising method treat nephropathy.Overactivation plays crucial role development DN. Our aim verify STZ-induced The modulated therapy may provide