Molecular mechanisms of proximal tubule cell endocytosis and its pathological roles in the development of chronic kidney disease
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 |
Section | 一般 |
Research Field |
Kidney internal medicine
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Research Institution | Niigata University |
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 |
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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Report
(4 results)
Research Products
(91 results)
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[Journal Article] Analysis of different complexes of type IIa sodium-dependent phosphate transporter in rat renal cortex using blue-native polyacrylamide gel electrophoresis2011
Author(s)
Tanimura A, Yamada F, Saito A, Ito M, Kimura T, Anzai N, Horie D, Yamamoto H, Miyamoto K, Taketani Y, Takeda E
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Journal Title
J Med Invest.
Volume: Vol.58(1, 2)
Pages: 140-147
Related Report
Peer Reviewed
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[Journal Article] Analysis of different complex of type IIa sodium-dependent phosphate transporter in rat renal cortex blue-native plyacrvlamide gel electrophoresis2011
Author(s)
Tanimura A, Yamada F, Saito A, Ito M, Kimura T, Anzai N, Horie D, Yamamoto H, Miyamoto K, Taketani Y, Takeda E
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Journal Title
J Med Invest
Volume: 58
Pages: 140-147
Related Report
Peer Reviewed
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[Presentation] Significance of urinary full-length and ectodomain forms of megalin in patients with type 2 diabetes2011
Author(s)
Ogasawara S, Hosojima M, Kabasawa H, Kaseda R, Yamamoto-Kabasawa K, Sato H, Takeda T, Suzuki Y, Narita I, Yamagata K, Tomino Y, Gejyo F, Hirayama Y, Sekine S, Saito A
Organizer
2011 Forefronts Symposium-Forefronts in Nephrology
Place of Presentation
Aahus Denmark
Related Report
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[Presentation] 2型糖尿病における尿中全長型および細胞外領域型メガリンの測定の意義2011
Author(s)
斉藤亮彦,小笠原真也,細島康宏,忰田亮平,蒲澤秀門,山本-蒲澤佳子,佐藤博慶,黒澤寛之,竹田徹朗,鈴木芳樹,成田一衛,山縣邦弘,富野康日己,下条文武,平山吉朗,関根盛
Organizer
日本プロテオーム学会2011年会
Place of Presentation
新潟
Related Report
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[Presentation] 培養近位尿細管上皮細胞におけるLPS-TNFα-ERK1/2シグナル経路を介したメガリンの発現調節機構2011
Author(s)
佐藤博慶,竹山綾,蒲澤秀門,長江多恵子,金子麗華,樋口文恵,鈴木哲世,山本佳子,細島康宏,竹田徹朗,鈴木芳樹,成田一衛,斉藤亮彦
Organizer
第54回日本腎臓学会学術総会
Place of Presentation
神奈川横浜市
Related Report
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[Presentation] 第54回日本糖尿病学会年次学術集会2011
Author(s)
斉藤亮彦,竹山綾,佐藤博慶,蒲澤秀門,長江多恵子,金子麗華,樋口文恵,鈴木哲世,山本佳子,細島康宏,忰田亮平,飯野則昭,竹田徹朗,鈴木芳樹,成田一衛
Organizer
培養近位尿細管細胞におけるLPS-TNFα-ERK1/2シグナル経路を介したメガリンの発現調節機構
Place of Presentation
北海道
Related Report
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[Presentation] メタボリックシンドローム関連腎症の発症・進展機序におけるメガリンの関与2010
Author(s)
佐藤博慶,笹川泰司,蒲澤秀門,飯野則昭,鈴木哲世,金子麗華,青木弘行,樋口文恵,鈴木芳樹,成田一衛,斉藤亮彦
Organizer
第22回日本糖尿病性腎症研究会
Place of Presentation
東京
Related Report
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[Presentation] Blue Native-PAGE法を用いたメガリンをめぐる分子間相互作用の検討2010
Author(s)
佐藤博慶,塩田友也,保坂聖子,蒲澤秀門,山本佳子,鈴木哲世,相馬多恵子,飯野則昭,竹田徹朗,成田一衛,斉藤亮彦
Organizer
第53回日本腎臓学会学術総会
Place of Presentation
兵庫
Related Report
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[Presentation] 尿中メガリンELISA測定系の構築とCKD評価における有用性2010
Author(s)
小笠原真也,黒澤寛之,竹田徹朗,飯野則昭,佐藤博慶,鈴木芳樹,淺沼克彦,富野康日己,山縣邦弘,成田一衛,下条文武,平山吉郎,関根盛,斉藤亮彦
Organizer
第53回日本腎臓学会学術総会
Place of Presentation
兵庫
Related Report
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[Presentation] Urinary shedding forms of megalin as novel biomarkers of proximal tubular injury, ISN Nexus-The Kidney and the Vascular System : Emerging Culprits in Pathogenesis and Advances in Therapy2010
Author(s)
Saito A, Ogasawara S, Kurosawa H, Takeda T, Iino N, Sato H, Suzuki Y, Asanuma K, Tomino Y, Narita I, Gejyo F, Hirayama Y, Sekine S
Place of Presentation
Kyoto
Related Report
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[Presentation] Urinary shedding forms of megalin as novel biomarkers of proximal tubular iniury2010
Author(s)
Saito A, Ogasawara S, Kurosawa H, Takeda T, Iino N, Sato H, Suzuki Y, Asanuma R, Tomino Y, Narita I, Gelyo F, Hirayama Y, Sekine S
Organizer
ISN Nexus-The Kidney and the Vascular System : Emerging Culprits in Pathogenesis and Advances in Therapy
Place of Presentation
Kyoto, Japan
Related Report
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[Presentation] 尿中メガリンEL ISA測定系の構築とCKD評価における有用性2010
Author(s)
小笠原真也, 黒澤寛之, 竹田徹里, 飯野則昭, 佐藤博慶, 鈴木芳樹, 淺沼克彦, 富野康日己, 山縣邦弘, 成田一衛, 下条文武, 平山吉郎, 関根盛, 斉藤亮彦
Organizer
第53回日本腎臓学会学術総会
Place of Presentation
兵庫県神戸市
Related Report
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[Presentation] B1ue Native-PAGE法を用いたメガリンをめぐる分子間相互作用の検討2010
Author(s)
佐藤博慶, 塩田友也, 保坂聖子, 蒲澤秀門, 山本佳子, 鈴木哲世, 相馬多恵子, 飯野則昭, 竹田徹朗, 成田一衛, 斉藤亮彦
Organizer
第53回日本腎臓学会学術総会
Place of Presentation
兵庫県 神戸市
Related Report
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[Presentation] Establishment of ELISA system to evaluate ectodomain and full-length forms of megalin shed in human urine2009
Author(s)
Ogasawara S, Kurosawa H, Takeda T, Iino N, Sato H, Suzuki Y, Asanuma K, Tomino Y, Yamagata K, Narita I, Gejyo F, Hirayama Y, Sekine S and Saito A
Organizer
Renal Week 2009
Place of Presentation
San Diego CA US
Related Report
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[Presentation] LPSによる培養近位尿細管細胞におけるmegalinの発現調節2009
Author(s)
竹山綾,佐藤博慶,相馬多恵子,蒲澤秀門,山本佳子,笹川泰司,飯野則昭,竹田徹朗,鈴木芳樹,下条文武,斉藤亮彦
Organizer
第52回日本腎臓学会学術総会
Place of Presentation
神奈川
Related Report
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[Presentation] マウス近位尿細管におけるMegalinを介したタンパク取り込みのin vivoイメージング2009
Author(s)
生山健児,蒲澤秀門,佐藤博慶,山本佳子,竹山綾,笹川泰司,細島康宏,飯野則昭,竹田徹朗,鈴木芳樹,追手巍,下条文武,斉藤亮彦
Organizer
第52回日本腎臓学会学術総会
Place of Presentation
神奈川
Related Report
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[Presentation] Megalin, Cubilin, Amnionless遺伝子安定発現MDCK細胞の樹立2009
Author(s)
鈴木哲世,竹田徹朗,佐藤博慶,笹川泰司,蒲澤秀門,竹山綾,山本佳子,細島康宏,相馬多恵子,飯野則昭,鈴木芳樹,下条文武,斉藤亮彦
Organizer
第52回日本腎臓学会学術総会
Place of Presentation
神奈川
Related Report
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[Presentation] 培養近位尿細管上皮細胞におけるGlucose, Insulin, EGF, Ang IIによるMegalinの発現調節機構2009
Author(s)
佐藤博慶,山本佳子,細島康宏,相馬多恵子,鈴木哲世,蒲澤秀門,竹山綾,笹川泰司,生山健児,塩田友也,飯野則昭,竹田徹朗,鈴木芳樹,下条文武,斉藤亮彦
Organizer
第52回日本腎臓学会学術総会
Place of Presentation
神奈川
Related Report
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