ArticleJournal of the American Society of Nephrology : JASN2016
Modulation of Polycystic Kidney Disease Severity by Phosphodiesterase 1 and 3 Subfamilies.
Article in Journal of the American Society of Nephrology : JASN, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed, 39 citations in OpenAlex.
- Modeling Complex Developmental Disease: The Case of Polycystic Kidney Disease.Journal of developmental biology · 2026Review
- A heteromeric TRP channel that functions as a WNT-activated G protein-coupled receptor.Nature communications · 2026Article
- Renal tissue-resident macrophages promote cystogenesis in early polycystic kidney disease.Journal of cell science · 2025Article
- Transforming advancing autosomal dominant polycystic kidney disease care: investigating new horizons in treatment and research.Inflammopharmacology · 2025Review
- Autosomal Dominant Polycystic Kidney Disease: From Pathogenesis to Organoid Disease Models.Biomedicines · 2025Review
- Physiologic mechanisms underlying polycystic kidney disease.Physiological reviews · 2025Review
- Article
- Review
- Emerging therapies for autosomal dominant polycystic kidney disease with a focus on cAMP signaling.Frontiers in molecular biosciences · 2022Review
- Polycystic Liver Disease: Pathophysiology, Diagnosis and Treatment.Hepatic medicine : evidence and research · 2022Review
- "ADPKD-omics": determinants of cyclic AMP levels in renal epithelial cells.Kidney international · 2022Review
- Recent advances in understanding ion transport mechanisms in polycystic kidney disease.Clinical science (London, England : 1979) · 2021Review
- Nephronophthisis-Pathobiology and Molecular Pathogenesis of a Rare Kidney Genetic Disease.Genes · 2021Review
- Modulation of polycystic kidney disease by G-protein coupled receptors and cyclic AMP signaling.Cellular signalling · 2020Review
- Machine learning guided association of adverse drug reactions with in vitro target-based pharmacology.EBioMedicine · 2020Article
- Synthesis and Modeling Studies of Furoxan Coupled Spiro-Isoquinolino Piperidine Derivatives as NO Releasing PDE 5 Inhibitors.Biomedicines · 2020Article
- Selective Phosphodiesterase 1 Inhibitor BTTQ Reduces Blood Pressure in Spontaneously Hypertensive and Dahl Salt Sensitive Rats: Role of Peripheral Vasodilation.Frontiers in physiology · 2020Article
- The pathobiology of polycystic kidney disease from a metabolic viewpoint.Nature reviews. Nephrology · 2019Review
- Precision gene editing technology and applications in nephrology.Nature reviews. Nephrology · 2018Review
- Expanding the role of vasopressin antagonism in polycystic kidney diseases: From adults to children?Pediatric nephrology (Berlin, Germany) · 2018Review
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Authors and funding
14 authors at 6 institutions in 1 country.
Funding
Abstract
Aberrant intracellular calcium levels and increased cAMP signaling contribute to the development of polycystic kidney disease (PKD). cAMP can be hydrolyzed by various phosphodiesterases (PDEs). To examine the role of cAMP hydrolysis and the most relevant PDEs in the pathogenesis of PKD, we examined cyst development in Pde1- or Pde3-knockout mice on the Pkd2(-/WS25) background (WS25 is an unstable Pkd2 allele). These PDEs were selected because of their importance in cross-talk between calcium and cyclic nucleotide signaling (PDE1), control of cell proliferation and cystic fibrosis transmembrane conductance regulator (CFTR) -driven fluid secretion (PDE3), and response to vasopressin V2 receptor activation (both). In Pkd2(-/WS25) mice, knockout of Pde1a, Pde1c, or Pde3a but not of Pde1b or Pde3b aggravated the development of PKD and was associated with higher levels of protein kinase A-phosphorylated (Ser133) cAMP-responsive binding protein (P-CREB), activating transcription factor-1, and CREB-induced CRE modulator proteins in kidney nuclear preparations. Immunostaining also revealed higher expression of P-CREB in Pkd2(-/) (WS25);Pde1a(-/-), Pkd2(-) (/WS25);Pde1c(-/-), and Pkd2(-/) (WS25);Pde3a(-/-) kidneys. The cystogenic effect of desmopressin administration was markedly enhanced in Pkd2(-/WS25);Pde3a(-/-) mice, despite PDE3 accounting for only a small fraction of renal cAMP PDE activity. These observations show that calcium- and calmodulin-dependent PDEs (PDE1A and PDE1C) and PDE3A modulate the development of PKD, possibly through the regulation of compartmentalized cAMP pools that control cell proliferation and CFTR-driven fluid secretion. Treatments capable of increasing the expression or activity of these PDEs may, therefore, retard the development of PKD.
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