Novel serpinopathy in rat kidney and pancreas induced by overexpression of megsin
| Autor: | Kiyoshi Kurokawa, Kiyokazu Nakazato, Yasuhiko Ueda, Toshio Miyata, Charles van Ypersele de Strihou, Satoru Takahashi, Hiroshi Onogi, Yuko Izuhara, Masayuki Yamamoto, Daisuke Suzuki, Reiko Inagi, Nobuteru Usuda, Akira Shimizu, Masaomi Nangaku, Hisashi Oishi |
|---|---|
| Rok vydání: | 2005 |
| Předmět: |
Nephrology
medicine.medical_specialty Pathology Immunoelectron microscopy Gene Expression Biology Serpin Kidney Animals Genetically Modified Internal medicine medicine In Situ Nick-End Labeling Animals Humans Rats Wistar Pancreas In Situ Hybridization Serpins geography geography.geographical_feature_category Endoplasmic reticulum Pancreatic Diseases General Medicine Islet medicine.disease Molecular biology Rats medicine.anatomical_structure Female Kidney Diseases Kidney disease |
| Zdroj: | Journal of the American Society of Nephrology : JASN. 16(5) |
| ISSN: | 1046-6673 |
| Popis: | The intracellular polymerization of abnormal serine protease inhibitors (serpins) results in liver or neuronal cell abnormalities recently identified as "serpinopathies." It was demonstrated in transgenic rats that overexpression of megsin, a recently discovered serpin located in the kidney, produces renal and pancreatic lesions characteristic of serpinopathies. Megsin expression is elevated in a variety of organs, including kidney and pancreas. Periodic acid-Schiff-positive, diastase-resistant intracellular inclusions develop only in the kidney and the pancreas. They correspond to electron-dense deposits, shown to contain megsin by immunohistochemistry and immunoelectron microscopy. In the kidney, inclusions are located mainly in the endoplasmic reticulum of glomerular epithelial, distal, and collecting duct cells, and are associated with massive proteinuria and an impaired renal function. In the pancreas, similar inclusions are found in the exocrine and Langerhans islet cells, where islet beta cells are reduced as a result of apoptosis. They are associated with diabetes with low insulin levels. The animals have an impaired growth and die within 10 wk. Rats that overexpress a mutant megsin, characterized by a deficient conformational transition activity, do not develop the serpinopathy, suggesting that some conformational flexibility of the serpin is required for the development of serpinopathy. This model of serpinopathy is the first to involve the kidney and the pancreas. |
| Databáze: | OpenAIRE |
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