Pathophysiological significances of ER stress in the kidney : A lesson from novel renal failure model rats
| Project/Area Number |
17590848
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Kidney internal medicine
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| Research Institution | Tokai University |
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Principal Investigator |
INAGI Reiko Tokai University, Medical Research Instiute, Associate Professor, 総合医学研究所, 助教授 (50232509)
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| Project Period (FY) |
2005 – 2006
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| Project Status |
Completed (Fiscal Year 2006)
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| Budget Amount *help |
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2006: ¥1,300,000 (Direct Cost: ¥1,300,000)
Fiscal Year 2005: ¥2,200,000 (Direct Cost: ¥2,200,000)
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| Keywords | endoplasmic reticulum / podocytes / serpinopathy / misfolding proteins / megsin / proteinuria / transgenic rats / hyperglycemia / トランスジェニックラット |
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| Research Abstract |
An imbalance between protein load and folding capacity is referred to as endoplasmic reticulum (ER) stress. ER stress is known to be related to progression of some protein conformational diseases such as neuronal disorder and diabetes mellitus. However a role of ER stress in the kidney diseases is still unclear yet. In this study, we evaluate pathophysiological significances of ER stress in the kidney.
In transgenic rats overexpressing megsin, a recently discovered renal serine protease inhibitor (serpin), renal lesions characteristic of serpinopathies, caused by the intracellular polymerization of abnormal serpins, were observed. Large amount of megsin was polymerized and formed intracellular inclusions mainly in the ER of glomerular epithelial and distal tubular cells of megsin transgenic rats. These phenomena were associated with proteinuria. The ER stress level was markedly increased in podocytes of megsin transgenic rats, and subsequently developed podocyte injury. In contrast, rats overexpressing a mutant megsin, characterized by a deficient conformational transition activity, did not develop the serpinopathy associated with renal dysfunction, proteinuria, and ER stress.
In experimental nephrosis rats, we demonstrated that ER stress was induced in the tubular cells exposed to proteinuria followed by apoptosis. Our in vitro study utilizing cultured rat tubular cells also showed that exposure to high concentration of albumin induced ER stress associated with apoptosis in these cells.
These results suggest for the first time pathophysiological significances of ER stress in renal diseases.
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Report
(3 results)
Research Products
(53 results)
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[Journal Article] Protective Role of Hypoxia-Inducible Factor-2{alpha} against Ischemic Damage and Oxidative Stress in the Kidney.2007
Author(s)
Kojima I, Tanaka T, Inagi R, Kato H, Yamashita T, Sakiyama A, Ohneda O, Takeda N, Sata M, Miyata T, Fujita T, Nangaku M.
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Journal Title
J Am Soc Nephrol. (in press)
Description
「研究成果報告書概要(欧文)」より
Related Report
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[Journal Article] A rat model of human FENIB (familial encephalopathy with neuroserpin inclusion bodies).2006
Author(s)
Takano K, Kitao Y, Inagi R, Momoi T, Matsuyama T, Miyata T, Yoneda Y, Iso H, Stern DM, Hori O, Ogawa S.
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Journal Title
Biochem Biophys Res Commun. 346(3)
Pages: 1040-1047
NAID
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Novel serpinopathy in rat kidney and pancreas induced by overexpression of megsin.2005
Author(s)
Inagi R, Nangaku M, Usuda N, Shimizu A, Onogi H, Izuhara Y, Nakazato K, Ueda Y, Oishi H, Takahashi S, Yamamoto M, Suzuki D, Kurokawa K, van Ypersele de Strihou C, Miyata T.
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Journal Title
J Am Soc Nephrol. 16(5)
Pages: 1339-1349
Description
「研究成果報告書概要(欧文)」より
Related Report
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