ArticlePurinergic signalling2016
P2Y2R is a direct target of HIF-1α and mediates secretion-dependent cyst growth of renal cyst-forming epithelial cells.
Article in Purinergic signalling, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 31 citations in OpenAlex.
- HIF-Regulated Pannexin-1 Channel Drives Luminal ATP Accumulation in Kidney Cysts.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2026Article
- Purinergic Receptor P2Y2 Activity Prevents DNA Damage in CClJournal of cellular biochemistry · 2025Article
- Clopidogrel protects against gentamicin-induced nephrotoxicity through targeting oxidative stress, apoptosis, and coagulation pathways.Naunyn-Schmiedeberg's archives of pharmacology · 2025Article
- Effects of Suramin on Polycystic Kidney Disease in a Mouse Model of Polycystin-1 Deficiency.International journal of molecular sciences · 2022Article
- Article
- Emerging therapies for autosomal dominant polycystic kidney disease with a focus on cAMP signaling.Frontiers in molecular biosciences · 2022Review
- Role of the Purinergic P2Y2 Receptor in Pulmonary Hypertension.International journal of environmental research and public health · 2021Review
- The chloride channel CFTR is not required for cyst growth in an ADPKD mouse model.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2021Article
- Gender-Dependent Phenotype in Polycystic Kidney Disease Is Determined by Differential Intracellular CaInternational journal of molecular sciences · 2021Article
- P2Y2R contributes to the development of diabetic nephropathy by inhibiting autophagy response.Molecular metabolism · 2020Article
- Macrophage migration inhibitory factor is regulated by HIF-1α and cAMP and promotes renal cyst cell proliferation in a macrophage-independent manner.Journal of molecular medicine (Berlin, Germany) · 2020Article
- Hypoxia-Inducible Factor and Oxygen Biology in the Kidney.Kidney360 · 2020Review
- Cyst growth in ADPKD is prevented by pharmacological and genetic inhibition of TMEM16A in vivo.Nature communications · 2020Article
- Modulation of polycystic kidney disease by G-protein coupled receptors and cyclic AMP signaling.Cellular signalling · 2020Review
- TMEM16A drives renal cyst growth by augmenting CaJournal of molecular medicine (Berlin, Germany) · 2020Article
- Increased Purinergic Responses Dependent on P2Y2 Receptors in Hepatocytes from CClInternational journal of molecular sciences · 2020Article
- Extracellular Nucleotides and P2 Receptors in Renal Function.Physiological reviews · 2020Review
- Lipid Peroxidation Drives Renal Cyst GrowthJournal of the American Society of Nephrology : JASN · 2019Article
- Characterization of purinergic receptor expression in ARPKD cystic epithelia.Purinergic signalling · 2018Article
- P2Y2R Signaling Is Involved in the Onset of Glomerulonephritis.Frontiers in immunology · 2018Article
Corrections and comments
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Authors and funding
11 authors at 4 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Polycystic kidney diseases are characterized by numerous renal cysts that continuously enlarge resulting in compression of intact nephrons and tissue hypoxia. Recently, we have shown that hypoxia-inducible factor (HIF)-1α promotes secretion-dependent cyst expansion, presumably by transcriptional regulation of proteins that are involved in calcium-activated chloride secretion. Here, we report that HIF-1α directly activates expression of the purinergic receptor P2Y2R in human primary renal tubular cells. In addition, we found that P2Y2R is highly expressed in cyst-lining cells of human ADPKD kidneys as well as PKD1 orthologous mouse kidneys. Knockdown of P2Y2R in renal collecting duct cells inhibited calcium-dependent chloride secretion in Ussing chamber analyses. In line with these findings, knockdown of P2Y2R retarded cyst expansion in vitro and prevented ATP- and HIF-1α-dependent cyst growth. In conclusion, P2Y2R mediates ATP-dependent cyst growth and is transcriptionally regulated by HIF-1α. These findings provide further mechanistic evidence on how hypoxia promotes cyst growth.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.