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

• Subject Area: Anatomy and Physiology ; Endocrinology, Diabetology, Metabolism ; Nephrology ; Pharmacology
• Term: Funded in 2023
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 394046635

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.

• DFG Programme: Collaborative Research Centres
• Subproject of: SFB 1365: Renoprotection
• Applicant Institution: shared FU Berlin and HU Berlin through:; Charité - Universitätsmedizin Berlin
• Project Heads: Natalia Alenina, Ph.D.; Professor Dr. Michael Bader; Privatdozent Dr. Enno Klußmann