Inhibition of Intrahepatic Bile Duct Dilation of the Polycystic Kidney Rat with a Novel Tyrosine Kinase Inhibitor Gefitinib
| Autor: | Kumiko Isse, Satoru Ozaki, Motoko Sasaki, Mitsue Yasoshima, Yasuni Nakanuma, Takahiro Sanzen, Shinichi Furubo, Yasunori Sato, Kenichi Harada, Kazuo Kizawa |
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| Jazyk: | angličtina |
| Rok vydání: | 2006 |
| Předmět: |
medicine.medical_specialty
medicine.drug_class Biliary Cyst Intrahepatic bile ducts Tyrosine-kinase inhibitor Pathology and Forensic Medicine Gefitinib Internal medicine medicine Polycystic kidney disease Animals Cyst Epidermal growth factor receptor Protein Kinase Inhibitors Mitogen-Activated Protein Kinase 7 Polycystic Kidney Diseases Mitogen-Activated Protein Kinase 3 biology Liver Diseases medicine.disease Autosomal Recessive Polycystic Kidney Disease Rats ErbB Receptors Disease Models Animal Endocrinology Bile Ducts Intrahepatic Liver biology.protein Quinazolines medicine.drug Regular Articles Dilatation Pathologic |
| Popis: | The polycystic kidney (PCK) rat represents a liver and kidney cyst pathology corresponding to Caroli's disease with congenital hepatic fibrosis and autosomal recessive polycystic kidney disease. We previously reported that an epidermal growth factor receptor tyrosine kinase inhibitor, gefitinib (Iressa), significantly inhibited the abnormal growth of biliary epithelial cells of PCK rats in vitro. This study investigated the effects of gefitinib on cyst pathogenesis of the PCK rat both in vitro and in vivo. A three-dimensional culture model of biliary epithelial cells in the collagen gel matrix was used for in vitro analysis. For in vivo experiments, PCK and control rats were treated with gefitinib between 3 and 10 weeks of age. In vitro, gefitinib had strong inhibitory effects on biliary cyst formation of PCK rats. In vivo, treatment with gefitinib significantly inhibited the cystic dilatation of the intrahepatic bile ducts of PCK rats, which was accompanied by improvement of liver fibrosis. By contrast, no beneficial effects were observed on renal cyst development because of the treatment. These results suggest that signaling pathways mediated by epidermal growth factor receptor are involved in biliary dysgenesis of the PCK rat, with the mechanisms of cyst progression being different between the liver and kidney. |
| Databáze: | OpenAIRE |
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