ArticleKidney international2018
Adenylyl cyclase 5 deficiency reduces renal cyclic AMP and cyst growth in an orthologous mouse model of polycystic kidney disease.
Article in Kidney international, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers.
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Who cites it
38 citing papers in PubMed, 48 citations in OpenAlex.
- Kidney-specific deletion of the BicC family RNA-binding protein 1 triggers an ADPKD-like cystogenic program.iScience · 2026Article
- Patient-derived kidney organoids recapitulate ADPKD and facilitate the identification of Rho pathway inhibitors as candidate therapeutics.Cell reports. Medicine · 2026Article
- A heteromeric TRP channel that functions as a WNT-activated G protein-coupled receptor.Nature communications · 2026Article
- Abnormal purinergic signaling contributes to development of renal cysts in autosomal dominant polycystic kidney disease.Purinergic signalling · 2026Article
- Lack of ANKMY2 suppresses kidney cystogenesis in embryonic- and adult-onset polycystic kidney disease.PLoS genetics · 2025Article
- Renal tissue-resident macrophages promote cystogenesis in early polycystic kidney disease.Journal of cell science · 2025Article
- Autosomal Dominant Polycystic Kidney Disease: From Pathogenesis to Organoid Disease Models.Biomedicines · 2025Review
- Physiologic mechanisms underlying polycystic kidney disease.Physiological reviews · 2025Review
- Autosomal Dominant Polycystic Kidney Disease and Idiopathic Arginine Vasopressin Deficiency: A Peculiar Case Report of Accelerated Kidney Function Decline.Canadian journal of kidney health and disease · 2025Article
- Targeted therapy of kidney disease with nanoparticle drug delivery materials.Bioactive materials · 2024Review
- Glis2 is an early effector of polycystin signaling and a target for therapy in polycystic kidney disease.Nature communications · 2024Article
- The role of N-methyladenosine modification in acute and chronic kidney diseases.Molecular medicine (Cambridge, Mass.) · 2023Review
- Compartmentalised cAMP signalling in the primary cilium.Frontiers in physiology · 2023Review
- Enhancer and super-enhancer landscape in polycystic kidney disease.Kidney international · 2023Article
- PKD1 and PKD2 mRNA cis-inhibition drives polycystic kidney disease progression.Nature communications · 2022Article
- Article
- Physiological roles of mammalian transmembrane adenylyl cyclase isoforms.Physiological reviews · 2022Review
- Regenerative Calcium Currents in Renal Primary Cilia.Frontiers in physiology · 2022Article
- "ADPKD-omics": determinants of cyclic AMP levels in renal epithelial cells.Kidney international · 2022Review
- Cilia-Localized Counterregulatory Signals as Drivers of Renal Cystogenesis.Frontiers in molecular biosciences · 2022Review
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6 authors at 4 institutions in 2 countries.
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Abstract
Cyclic AMP promotes cyst growth in polycystic kidney disease (PKD) by stimulating cell proliferation and fluid secretion. Previously, we showed that the primary cilium of renal epithelial cells contains a cAMP regulatory complex comprising adenylyl cyclases 5 and 6 (AC5/6), polycystin-2, A-kinase anchoring protein 150, protein kinase A, and phosphodiesterase 4C. In Kif3a mutant cells that lack primary cilia, the formation of this regulatory complex is disrupted and cAMP levels are increased. Inhibition of AC5 reduces cAMP levels in Kif3a mutant cells, suggesting that AC5 may mediate the increase in cAMP in PKD. Here, we examined the role of AC5 in an orthologous mouse model of PKD caused by kidney-specific ablation of Pkd2. Knockdown of AC5 with siRNA attenuated the increase in cAMP levels in Pkd2-deficient renal epithelial cells. Levels of cAMP and AC5 mRNA transcripts were elevated in the kidneys of mice with collecting duct-specific ablation of Pkd2. Compared with Pkd2 single mutant mice, AC5/Pkd2 double mutant mice had less kidney enlargement, lower cyst index, reduced kidney injury, and improved kidney function. Importantly, cAMP levels and cAMP-dependent signaling were reduced in the kidneys of AC5/Pkd2 double mutant compared to the kidneys of Pkd2 single mutant mice. Additionally, we localized endogenous AC5 in the primary cilium of renal epithelial cells and showed that ablation of AC5 reduced ciliary elongation in the kidneys of Pkd2 mutant mice. Thus, AC5 contributes importantly to increased renal cAMP levels and cyst growth in Pkd2 mutant mice, and inhibition of AC5 may be beneficial in the treatment of PKD.
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