Activation of Phosphatidylinositol-3 Kinase Regulates Pancreatic Duodenal Homeobox-1 in Duct Cells During Pancreatic Regeneration
| Autor: | Haruto Nishimura, Junji Ueda, Hiroshi Saito, B. Mark Evers, Hiroaki Watanabe |
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| Rok vydání: | 2008 |
| Předmět: |
Male
endocrine system Time Factors Endocrinology Diabetes and Metabolism Cellular differentiation Blotting Western Phosphatidylinositol 3-Kinases Biology Article Wortmannin Mice chemistry.chemical_compound Pancreatectomy Endocrinology Internal Medicine medicine Animals Insulin Regeneration Phosphatidylinositol Phosphorylation RNA Small Interfering Pancreas Protein Kinase Inhibitors PI3K/AKT/mTOR pathway Cell Proliferation Phosphoinositide-3 Kinase Inhibitors Homeodomain Proteins Hepatology Kinase Pancreatic Ducts Cell Differentiation Immunohistochemistry Androstadienes Enzyme Activation Mice Inbred C57BL medicine.anatomical_structure chemistry Trans-Activators Cancer research RNA Interference Signal transduction Proto-Oncogene Proteins c-akt Signal Transduction |
| Zdroj: | Pancreas. 36:153-159 |
| ISSN: | 0885-3177 |
| Popis: | The purpose of our study was to determine whether the phosphatidylinositol 3-kinase (PI3K)/Akt pathway contributes to expression of pancreatic duodenal homeobox-1 (PDX-1) in duct cells and the cell differentiation during pancreatic regeneration.The role of PI3K in PDX-1 expression and duct cell differentiation with pancreatic regeneration in mice after partial pancreatectomy (Px) was examined using either wortmannin, a pharmacological PI3K inhibitor, or small-interfering RNA directed to the p85alpha regulatory subunit of PI3K. Akt phosphorylation, a marker of PI3K activation, and PDX-1 expression were assessed by Western blot analysis and immunohistochemistry.Both PDX-1 levels and Akt phosphorylation were concomitantly increased in pancreatic ducts after partial Px and, conversely, blocked by treatment with wortmannin or p85alpha small-interfering RNA. Pancreatic duct cell differentiation, as assessed by appearance of insulin-positive cells 3 days after partial Px, was effectively reduced by wortmannin.The PI3K/Akt activation plays a critical role for both PDX-1 expression and pancreatic duct cell differentiation into insulin-producing cells during pancreatic regeneration. |
| Databáze: | OpenAIRE |
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