ArticleJournal of the American Society of Nephrology : JASN2013
TRPV4 dysfunction promotes renal cystogenesis in autosomal recessive polycystic kidney disease.
Article in Journal of the American Society of Nephrology : JASN, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 50 papers.
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Who cites it
50 citing papers in PubMed, 78 citations in OpenAlex.
- 25+ Years of TRPV4: From Discovery to Translational Horizons.Research square · 2026Article
- Review
- Comparative analysis ofbioRxiv : the preprint server for biology · 2025Article
- Identification and Properties of TRPV4 Mutant Channels Present in Polycystic Kidney Disease Patients.Function (Oxford, England) · 2024Article
- TRPV4 expression in the renal tubule is necessary for maintaining whole body KAmerican journal of physiology. Renal physiology · 2023Article
- TRPV4 functional status in cystic cells regulates cystogenesis in autosomal recessive polycystic kidney disease during variations in dietary potassium.Physiological reports · 2023Article
- A comparative study of cellular diversity between the Xenopus pronephric and mouse metanephric nephron.Kidney international · 2023Article
- Following Ussing's legacy: from amphibian models to mammalian kidney and brain.American journal of physiology. Cell physiology · 2022Review
- Organoid-on-a-chip model of human ARPKD reveals mechanosensing pathomechanisms for drug discovery.Science advances · 2022Article
- Nephrotoxicity evaluation and proteomic analysis in kidneys of rats exposed to thioacetamide.Scientific reports · 2022Article
- Multiubiquitination of TRPV4 reduces channel activity independent of surface localization.The Journal of biological chemistry · 2022Article
- Emerging therapies for autosomal dominant polycystic kidney disease with a focus on cAMP signaling.Frontiers in molecular biosciences · 2022Review
- Regenerative Calcium Currents in Renal Primary Cilia.Frontiers in physiology · 2022Article
- 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
- With-No-Lysine Kinase 1 (WNK1) Augments TRPV4 Function in the Aldosterone-Sensitive Distal Nephron.Cells · 2021Article
- Inward CaAmerican journal of physiology. Renal physiology · 2021Article
- Modulation of polycystic kidney disease by G-protein coupled receptors and cyclic AMP signaling.Cellular signalling · 2020Review
- TRPV4: A Physio and Pathophysiologically Significant Ion Channel.International journal of molecular sciences · 2020Review
- Adenosine inhibits the basolateral ClAmerican journal of physiology. Renal physiology · 2020Article
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Authors and funding
6 authors at 1 institution in 1 country.
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Abstract
The molecular mechanism of cyst formation and expansion in autosomal recessive polycystic kidney disease (ARPKD) is poorly understood, but impaired mechanosensitivity to tubular flow and dysfunctional calcium signaling are important contributors. The activity of the mechanosensitive Ca(2+)-permeable TRPV4 channel underlies flow-dependent Ca(2+) signaling in murine collecting duct (CD) cells, suggesting that this channel may contribute to cystogenesis in ARPKD. Here, we developed a method to isolate CD-derived cysts and studied TRPV4 function in these cysts laid open as monolayers and in nondilated split-open CDs in a rat model of ARPKD. In freshly isolated CD-derived cyst monolayers, we observed markedly impaired TRPV4 activity, abnormal subcellular localization of the channel, disrupted TRPV4 glycosylation, decreased basal [Ca(2+)]i, and loss of flow-mediated [Ca(2+)]i signaling. In contrast, nondilated CDs of these rats exhibited functional TRPV4 with largely preserved mechanosensitive properties. Long-term systemic augmentation of TRPV4 activity with a selective TRPV4 activator significantly attenuated the renal manifestations of ARPKD in a time-dependent manner. At the cellular level, selective activation of TRPV4 restored mechanosensitive Ca(2+) signaling as well as the function and subcellular distribution of TRPV4. In conclusion, the functional status of TRPV4, which underlies mechanosensitive Ca(2+) signaling in CD cells, inversely correlates with renal cystogenesis in ARPKD. Augmenting TRPV4 activity may have therapeutic potential in ARPKD.
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