ArticleGastroenterology2012
Inhibition of Cdc25A suppresses hepato-renal cystogenesis in rodent models of polycystic kidney and liver disease.
Article in Gastroenterology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 39 citations in OpenAlex.
- 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
- Therapeutic advances in ADPKD: the future awaits.Journal of nephrology · 2022Review
- Polycystic Liver Disease: Advances in Understanding and Treatment.Annual review of pathology · 2022Review
- Inflammatory pathways and cholangiocarcinoma risk mechanisms and prevention.Advances in cancer research · 2022Review
- Autophagy-mediated reduction of miR-345 contributes to hepatic cystogenesis in polycystic liver disease.JHEP reports : innovation in hepatology · 2021Article
- Autosomal dominant polycystic kidney disease: Disrupted pathways and potential therapeutic interventions.Journal of cellular physiology · 2019Review
- Pathobiology of inherited biliary diseases: a roadmap to understand acquired liver diseases.Nature reviews. Gastroenterology & hepatology · 2019Review
- Combination of a Histone Deacetylase 6 Inhibitor and a Somatostatin Receptor Agonist Synergistically Reduces Hepatorenal Cystogenesis in an Animal Model of Polycystic Liver Disease.The American journal of pathology · 2018Article
- Cholangiocyte autophagy contributes to hepatic cystogenesis in polycystic liver disease and represents a potential therapeutic target.Hepatology (Baltimore, Md.) · 2018Article
- Cystic Kidney Diseases From the Adult Nephrologist's Point of View.Frontiers in pediatrics · 2018Review
- Increased YAP Activation Is Associated With Hepatic Cyst Epithelial Cell Proliferation in ARPKD/CHF.Gene expression · 2017Article
- TGR5 contributes to hepatic cystogenesis in rodents with polycystic liver diseases through cyclic adenosine monophosphate/Gαs signaling.Hepatology (Baltimore, Md.) · 2017Article
- Therapeutic Targets in Polycystic Liver Disease.Current drug targets · 2017Review
- Role and regulation of Cdc25A phosphatase in neuron death induced by NGF deprivation orCell death discovery · 2016Article
- Noninvasive monitoring of mouse renal allograft rejection using micro-CT.Annals of surgical treatment and research · 2015Article
- Polycystic liver diseases: advanced insights into the molecular mechanisms.Nature reviews. Gastroenterology & hepatology · 2014Review
- HDAC6 is overexpressed in cystic cholangiocytes and its inhibition reduces cystogenesis.The American journal of pathology · 2014Article
- Centrosomal abnormalities characterize human and rodent cystic cholangiocytes and are associated with Cdc25A overexpression.The American journal of pathology · 2014Article
- Hepatic loss of miR-122 predisposes mice to hepatobiliary cyst and hepatocellular carcinoma upon diethylnitrosamine exposure.The American journal of pathology · 2013Article
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Authors and funding
13 authors at 3 institutions in 2 countries.
Funding
Abstract
BACKGROUND &
aimsIn polycystic kidney disease and polycystic liver disease (PLD), the normally nonproliferative hepato-renal epithelia acquire a proliferative, cystic phenotype that is linked to overexpression of cell division cycle 25 (Cdc25)A phosphatase and cell-cycle deregulation. We investigated the effects of Cdc25A inhibition in mice and rats via genetic and pharmacologic approaches.
methodsCdc25A(+/-) mice (which have reduced levels of Cdc25A) were cross-bred with polycystic kidney and hepatic disease 1 (Pkhd1(del2/del2)) mice (which have increased levels of Cdc25A and develop hepatic cysts). Cdc25A expression was analyzed in livers of control and polycystic kidney (PCK) rats, control and polycystic kidney 2 (Pkd2(ws25/-)) mice, healthy individuals, and patients with PLD. We examined effects of pharmacologic inhibition of Cdc25A with vitamin K3 (VK3) on the cell cycle, proliferation, and cyst expansion in vitro; hepato-renal cystogenesis in PCK rats and Pkd2(ws25/-)mice; and expression of Cdc25A and the cell-cycle proteins regulated by Cdc25A. We also examined the effects of the Cdc25A inhibitor PM-20 on hepato-renal cystogenesis in Pkd2(ws25/-) mice.
resultsLiver weights and hepatic and fibrotic areas were decreased by 32%-52% in Cdc25A(+/-):Pkhd1(del2/del2) mice, compared with Pkhd1(del2/del2) mice. VK3 altered the cell cycle and reduced proliferation of cultured cholangiocytes by 32%-83% and decreased growth of cultured cysts by 23%-67%. In PCK rats and Pkd2(ws25/-) mice, VK3 reduced liver and kidney weights and hepato-renal cystic and fibrotic areas by 18%-34%. PM-20 decreased hepato-renal cystogenesis in Pkd2(ws25/-) mice by 15%.
conclusionsCdc25A inhibitors block cell-cycle progression and proliferation, reduce liver and kidney weights and cyst growth in animal models of polycystic kidney disease and PLD, and might be developed as therapeutics for these diseases.
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