Molecular mechanisms of PDE3A-mediated renoprotection (A06 (B03 + B06))

磷酸二酯酶PDE 3A基因突变导致高血压伴短指（HTNB）。令人惊讶的是，HTNB患者和我们的CRISPR/Cas9大鼠HTNB模型几乎不发生终末器官损伤，如CKD，尽管他们有高血压。我们的目的是提供深入了解突变PDE 3A肾保护的分子机制，建立细胞内，细胞类型和隔室特异性肾保护治疗。与肾脏损伤诱导双调蛋白，我们确定了一个候选人，其参与将被阐明。为了进一步分析，我们将使用我们的大鼠HTNB模型的肾脏的单细胞RNA测序、成像、生物化学和药理学方法。

Mutations in the phosphodiesterase PDE3A gene cause hypertension with brachydactyly (HTNB). Surprisingly, HTNB patients and our CRISPR/Cas9 rat HTNB models hardly develop end organ damage such as CKD, despite their hypertension. Our aim is providing insight into molecular mechanisms underlying mutant PDE3A renoprotection for establishing intracellular, cell type- and compartment-specific renoprotective therapy. With the kidney damage-inducing amphiregulin, we identified a candidate whose involvement will be elucidated. For further analyses, we will use single cell RNA sequencing of the kidneys of our rat HTNB models, imaging, biochemical and pharmacological approaches.