ArticleGastroenterology2010
Activation of Trpv4 reduces the hyperproliferative phenotype of cystic cholangiocytes from an animal model of ARPKD.
Article in Gastroenterology, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 62 papers.
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Who cites it
62 citing papers in PubMed, 96 citations in OpenAlex.
- Deciphering the Impact of RAC1-SPTAN1 in ARPKD Cystogenesis Using Multifaceted Models.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Primary Cilia in Hepatic Biliary Hyperplasia: Implications for Liver Diseases.Seminars in liver disease · 2025Review
- Review
- A miRNA-Based Approach in Autosomal Dominant Polycystic Kidney Disease: Challenges and Insights from Adult to Pediatric Evidence.Molecular diagnosis & therapy · 2025Review
- WNT signaling contributes to the extrahepatic bile duct proliferative response to obstruction in mice.JCI insight · 2024Article
- Identification and Properties of TRPV4 Mutant Channels Present in Polycystic Kidney Disease Patients.Function (Oxford, England) · 2024Article
- Clinical manifestation, epidemiology, genetic basis, potential molecular targets, and current treatment of polycystic liver disease.Orphanet journal of rare diseases · 2024Review
- Genetics, pathobiology and therapeutic opportunities of polycystic liver disease.Nature reviews. Gastroenterology & hepatology · 2022Review
- Dysregulation of the Scribble/YAP/β-catenin axis sustains the fibroinflammatory response in a PKHD1FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2022Article
- Physiological and Pathological Significance of Esophageal TRP Channels: Special Focus on TRPV4 in Esophageal Epithelial Cells.International journal of molecular sciences · 2022Review
- Therapeutic advances in ADPKD: the future awaits.Journal of nephrology · 2022Review
- Polycystic Liver Disease: Advances in Understanding and Treatment.Annual review of pathology · 2022Review
- 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
- The Biology of Vasopressin.Biomedicines · 2021Review
- Fibrocystic liver disease: novel concepts and translational perspectives.Translational gastroenterology and hepatology · 2021Review
- 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
- Role of Transient Receptor Potential Vanilloid 4 Channel in Skin Physiology and Pathology.Sultan Qaboos University medical journal · 2020Review
- Mechanosensor transient receptor potential vanilloid member 4 (TRPV4) regulates mouse cholangiocyte secretion and bile formation.American journal of physiology. Gastrointestinal and liver physiology · 2020Article
2 more citing papers are in PubMed but not listed here.
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Authors and funding
10 authors at 2 institutions in 3 countries.
Funding
Abstract
BACKGROUND &
aimsIn polycystic liver diseases, cyst formation involves cholangiocyte hyperproliferation. In polycystic kidney (PCK) rats, an animal model of autosomal-recessive polycystic kidney disease (ARPKD), decreased intracellular calcium [Ca(2+)](i) in cholangiocytes is associated with hyperproliferation. We recently showed transient receptor potential vanilloid 4 (Trpv4), a calcium-entry channel, is expressed in normal cholangiocytes and its activation leads to [Ca(2+)](i) increase. Thus, we hypothesized that pharmacologic activation of Trpv4 might reverse the hyperproliferative phenotype of PCK cholangiocytes.
methodsTrpv4 expression was examined in liver of normal and PCK rats, normal human beings, and patients with autosomal-dominant polycystic kidney disease or ARPKD. Trpv4 activation effect on cell proliferation and cyst formation was assessed in cholangiocytes derived from normal and PCK rats. The in vivo effects of Trpv4 activation on kidney and liver cysts was analyzed in PCK rats.
resultsTrpv4 was overexpressed both at messenger RNA (8-fold) and protein (3-fold) levels in PCK cholangiocytes. Confocal and immunogold electron microscopy supported Trpv4 overexpression in the livers of PCK rats and ARPKD or autosomal-dominant polycystic kidney disease patients. Trpv4 activation in PCK cholangiocytes increased [Ca(2+)](i) by 30%, inhibiting cell proliferation by approximately 25%-50% and cyst growth in 3-dimensional culture (3-fold). Trpv4-small interfering RNA silencing blocked effects of Trpv4 activators by 70%. Trpv4 activation was associated with Akt phosphorylation and beta-Raf and Erk1/2 inhibition. In vivo, Trpv4 activation induced a significant decrease in renal cystic area and a nonsignificant decrease in liver cysts.
conclusionsTaken together, our in vitro and in vivo data suggest that increasing intracellular calcium by Trpv4 activation may represent a potential therapeutic approach in PKD.
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