Abstract | BACKGROUND & AIMS: METHODS: We studied mice in which Pkd1 or Pkd2 were conditionally inactivated following exposure to tamoxifen; these mice were called Pkd1(flox/-):pCxCreER (Pkd1KO) and Pkd2(flox/-):pCxCreER (Pkd2KO). RESULTS: CONCLUSIONS: The PKA-ERK1/2- VEGF signaling pathway promotes growth of liver cysts in mice. In Pkd2-defective LCECs, PKA-dependent ERK1/2 signaling controls HIF-1alpha-dependent VEGF secretion and VEGFR-2 signaling. Autocrine and paracrine VEGF signaling promotes the growth of liver cysts in Pkd2KO mice. VEGF inhibitors might be used to treat patients with polycystic liver disease.
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Authors | Carlo Spirli, Stefano Okolicsanyi, Romina Fiorotto, Luca Fabris, Massimiliano Cadamuro, Silvia Lecchi, Xin Tian, Stefan Somlo, Mario Strazzabosco |
Journal | Gastroenterology
(Gastroenterology)
Vol. 138
Issue 1
Pg. 360-371.e7
(Jan 2010)
ISSN: 1528-0012 [Electronic] United States |
PMID | 19766642
(Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
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Copyright | Copyright 2010 AGA Institute. Published by Elsevier Inc. All rights reserved. |
Chemical References |
- Hif1a protein, mouse
- Hypoxia-Inducible Factor 1, alpha Subunit
- Indoles
- Proliferating Cell Nuclear Antigen
- Protein Kinase Inhibitors
- Pyrroles
- Repressor Proteins
- TRPP Cation Channels
- Tip30 protein, mouse
- Tumor Suppressor Proteins
- Vascular Endothelial Growth Factor A
- polycystic kidney disease 1 protein
- polycystic kidney disease 2 protein
- vascular endothelial growth factor A, mouse
- Semaxinib
- Vascular Endothelial Growth Factor Receptor-2
- Cyclic AMP-Dependent Protein Kinases
- Mitogen-Activated Protein Kinase 1
- Mitogen-Activated Protein Kinase 3
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Topics |
- Animals
- Cells, Cultured
- Cyclic AMP-Dependent Protein Kinases
(metabolism)
- Cysts
(metabolism, pathology, physiopathology)
- Hypoxia-Inducible Factor 1, alpha Subunit
(metabolism)
- Indoles
(pharmacology)
- Liver Diseases
(metabolism, pathology, physiopathology)
- MAP Kinase Signaling System
(physiology)
- Mice
- Mice, Knockout
- Mitogen-Activated Protein Kinase 1
(metabolism)
- Mitogen-Activated Protein Kinase 3
(metabolism)
- Phenotype
- Phosphorylation
(physiology)
- Proliferating Cell Nuclear Antigen
(metabolism)
- Protein Kinase Inhibitors
(pharmacology)
- Pyrroles
(pharmacology)
- Repressor Proteins
(metabolism)
- TRPP Cation Channels
(genetics)
- Tumor Suppressor Proteins
(metabolism)
- Vascular Endothelial Growth Factor A
(metabolism)
- Vascular Endothelial Growth Factor Receptor-2
(antagonists & inhibitors, metabolism)
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