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

高血压对慢性肾脏病进展的负面影响是巨大的。我们发现磷酸二酯酶3A(PDE3A)基因突变会导致孟德尔式高血压(HTNB)，但对肾功能几乎没有影响。我们的初步数据表明，突变的PDE3A异常地定位于细胞内，并改变了微域中的cAMP信号。我们现在已经产生了PDE3A激活的、PDE3A缺失的和产仔伴侣野生型(WT)的大鼠品系，以及一个转基因的Cre-PDE3A可激活的小鼠品系，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。这些保护机制构成了设计新的药理策略以有利地影响CKD过程的基础。

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.