2005 Fiscal Year Final Research Report Summary
Molecular mechanism of uremic toxin protein metabolism by megalin, an endocytic receptor, and its application to cell therapy
| Project/Area Number |
16590782
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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 | Niigata University |
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Principal Investigator |
SAITO Akihiko Niigata University, Graduate School of Medical and Dental Sciences, Associate professor, 大学院・医歯学総合研究科, 客員助教授 (80293207)
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| Co-Investigator(Kenkyū-buntansha) |
TAKEDA Tetsuro Niigata University, Medical and Dental Hospital, Assistant, 医歯学総合病院, 助手 (10361924)
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| Project Period (FY) |
2004 – 2005
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| Keywords | megalin / AGE / L-FABP / cell transplantation / uremic toxin protein / amniotic epithelial cell |
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| Research Abstract |
1. Megalin was found to be the proximal tubular endocytic receptor for leptin, an adipocytokine and a uremic toxin protein. So-called leptin receptor was localized in the various nephron segments by immunohistochemistry.
2. Megalin was found to directly bind advanced glycation endproducts (AGE), a uremic toxin protein, using quartz crystal microbalance analysis.
3. Megalin was found to act as an endocytic receptor for liver-type fatty acid binding protein (L-FABP) that is released from liver to the blood circulation, filtered by glomeruli and taken up by proximal tubule cells. L-FABP binds free fatty acids as well as various hydrophobic molecules, some of which are potentially nephrotoxic. It is much excreted to the circulation when liver is injured, indicating that it may play a role in the pathogenesis of renal disorders associated with liver injury. L-FABP may be increased in the circulation in renal failure and it may also act as a uremic toxin protein.
4. We reported a hypothesis indicating that renal protein metabolic overload via megalin may play a role in the pathogenesis of diabetic and metabolic syndrome-associated nephropathies. We also developed a method for measuring human urinary megalin (a patent applied).
5. We analyzed the function of amniotic epithelial cells that express megalin for the application to cell therary for uremic toxin protein metabolism in renal failure. We also succeeded in transient expression of rat full-length megalin cDNA in COS-7 cells, which would be useful for establishing cells permanently express megalin in the future by gene transfection.
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Research Products
(12 results)
