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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| Project Status |
Completed (Fiscal Year 2005)
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| Budget Amount *help |
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2005: ¥1,800,000 (Direct Cost: ¥1,800,000)
Fiscal Year 2004: ¥1,700,000 (Direct Cost: ¥1,700,000)
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| Keywords | megalin / AGE / L-FABP / cell transplantation / uremic toxin protein / amniotic epithelial cell / エンドサイトーシス / レプチン / Dent病 / キュビリン |
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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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Report
(3 results)
Research Products
(23 results)
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[Journal Article] Evidence for megalin-mediated proximal tubular uptake of L-FABP, a carrier of potentially nephrotoxic molecules.2005
Author(s)
Oyama Y, Takeda T, Hama H, Tanuma A, Iino N, Sato K, Kaseda R, Ma M, Yamamoto T, Fujii H, Kazama JJ, Odani S, Terada Y, Mizuta K, Gejyo F, Saito A
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Journal Title
Lab Invest 85
Pages: 522-531
Related Report
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[Journal Article] Role of megalin, a proximal tubular endocytotic receptor, in the pathogenesis of diabetic and metabolic syndrome-related nephropathies2005
Author(s)
Saito A, Takeda T, Hama H, Oyama Y, Sato K, Tanuma A, Kaseda R, Ueno M, Nishi S, Ogasawara S, Gondaira F, Suzuki Y, Gejyo F
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Journal Title
Related Report
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