Targeting PDE3A for protecting from hypertension-induced chronic kidney disease (B03)

靶向 PDE3A 预防高血压诱发的慢性肾病 (B03)

• 批准号: 418375148
• 金额: --
• 依托单位: Max-Delbrück-Centrum für Molekulare Medizin (MDC) in der Helmholtz-Gemeinschaft
• 依托单位国家: 德国
• 项目类别: Collaborative Research Centres
• 财政年份: 2019
• 资助国家: 德国
• 起止时间: 2018-12-31 至 2021-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/418375148?language=en
• 关键词: Targeting; PDE3A; protecting; hypertension; induced

The negative influence of hypertension on CKD progression is substantial. We identified mutations in the phosphodiesterase 3A (PDE3A) gene that cause a Mendelian form of hypertension (HTNB), but hardly affects kidney function. Our preliminary data indicate that mutant PDE3A is aberrantly located in cells and changes cAMP signaling in microdomains. We have now generated rat strains, PDE3A-activating, PDE3A-deleted, and litter-mate wild-type (WT), and a transgenic Cre-PDE3A-activatable mouse strain that will allow us to search for the protective changes and thus new renoprotective targets. The protective mechanisms form the basis for designing novel pharmacological strategies to favorably influence the course of CKD.

高血压对CKD进展的负面影响是巨大的。我们鉴定了磷酸二酯酶3A（PDE 3A）基因的突变，该突变导致孟德尔形式的高血压（HTNB），但几乎不影响肾功能。我们的初步数据表明，突变体PDE 3A是aberrantly位于细胞和改变cAMP信号的微域。我们现在已经产生了大鼠品系，PDE 3A激活，PDE 3A缺失，和同窝野生型（WT），和转基因Cre-PDE 3A激活小鼠品系，这将使我们能够寻找保护性变化，从而寻找新的肾脏保护靶点。保护机制形成了设计新的药理学策略以有利地影响CKD进程的基础。