| Project/Area Number |
21591023
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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 新潟大学, 大学院・医歯学総合研究科, 特任教授 (80293207)
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| Co-Investigator(Kenkyū-buntansha) |
SATO Hiroyoshi 新潟大学, 大学院・医歯学総合研究科, 特任助教 (30413610)
IINO Noriaki 新潟大学, 医歯学総合病院, 助教 (10420308)
TAKEDA Tetsuro 獨協医科大学, 医学部, 教授 (10361924)
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| Co-Investigator(Renkei-kenkyūsha) |
NISHIYAMA Akira 香川大学, 医学部, 教授 (10325334)
ICHIHARA Atsuhiro 東京女子医科大学, 医学部, 教授 (60203105)
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| Project Period (FY) |
2009 – 2011
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| Project Status |
Completed (Fiscal Year 2011)
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| Budget Amount *help |
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2011: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2010: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2009: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
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| Keywords | メガリン / 近位尿細管 / エンドサイトーシス / 慢性腎臓病 / レニン-アンジオテンシン系 / バイオマーカー / アンジオテンシノゲン / 糖尿病 / メタボリックシンドローム / エンドトキシン |
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| Research Abstract |
We analyzed molecular mechanisms of functions of megalin, an endocytic receptor in proximal tubule cells. We also established a novel megalin-related method for evaluating chronic kidney disease and investigated megalin-mediated mechanisms of the development of chronic kidney disease.
1) We found that megalin and nonmuscle myosin heavy chain IIA interact with the adaptor protein Disabled-2 in proximal tubule cells(Kidney Int 2009).
2) Endotoxins are increased in the serum of patients with type 2 diabetes and metabolic syndrome. We found that megalin is downregulated via LPS-TNF-α-ERK1/2 signaling pathway in proximal tubule cells(BBRC 2011).
3) We established ELISA systems to measure human megalin and showed that urinary megalin excretion is a useful biomarker for early diagnosis and evaluation of the severity of diabetic nephropathy and for analyzing cardiovascular risks(Diabetes Care 2012).
4) We found that liver-derived angiotensinogen is involved in the activation of the renin-angiotensin system(generation of angiotensin II) in the kidney and that glomerular-filtered angiotensinogen is taken up by megalin in proximal tubule cells(JASN 2012).
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