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MOLECULAR MECHANISMS OF ACTION AND PHYSIOLOGICAL ROLES OF LIPID AUTACOIDS IN THE NEPHRON

Research Project

Project/Area Number 07457239
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Kidney internal medicine
Research InstitutionUNIVERSITY OF TOKYO

Principal Investigator

WATANABE Tsuyoshi  University of Tokyo, Faculty of medicine, Associate professor, 医学部・附属病院, 助教授 (80158641)

Co-Investigator(Kenkyū-buntansha) 東郷 真子  東京大学, 保健センター, 医員
SEKI George  University of Tokyo, Faculty of medicine, Assistant Professor, 医学部・附属病院, 助手 (30206619)
TANIGUCHI Shigeo  University of Tokyo, Faculty of medicine, Assistant Professor, 医学部・附属病院, 助手 (50188380)
NAKAO Akihide  University of Tokyo, Faculty of medicine, Assistant Professor, 医学部・附属病院, 助手 (10159056)
HASHIMOTO Yoshiaki  University of Tokyo, Faculty of medicine, Lecturer, 医学部・附属病院, 講師 (40172879)
TOGO Masako  University of Tokyo, Faculty of medicine, Senior Resident
本田 善一郎  東京大学, 保健センター, 助手 (70238814)
Project Period (FY) 1995 – 1996
Project Status Completed (Fiscal Year 1996)
Budget Amount *help
¥7,300,000 (Direct Cost: ¥7,300,000)
Fiscal Year 1996: ¥2,500,000 (Direct Cost: ¥2,500,000)
Fiscal Year 1995: ¥4,800,000 (Direct Cost: ¥4,800,000)
Keywordsplatelet-activating factor receptor / thromboxane A_2 receptor / microdissection / nephron / RT-PCR / mRNA expression / glomerular mesangial cells / homologous down-regulation / 血小板活性化因子(PAF) / プロスタグランジン / MRT-PCR / micro-perfusion / mRNA定量 / 情報伝達 / 遺伝子多型
Research Abstract

In order to clarify the action mechanisms and physiological and pathophysiological significances of lipid autacoids such as platelet activating factor (PAF) and thromboxane (TX) A_2, we performed molecular and cellular biological studies in microdissected nephron segments from rodent kidneys, cultured renel-derived cells such as glomerular mesangial cells, genetically target mouse and DNA samples from patients with renal diseases, the results of which are as follows ; (1) Using our new quantitative RT-PCR method (MRT-PCR) in microdissected segments, we demonstrated ubiquitous distribution of PAF and TXA_2 receptor mRNA in the nephron, (2) homologous down-regulation of PAF receptor mRNA expression was shown to be mediated by cAMP formed though PAF-induced PGE_2 production in cultured mesangial cells, (3) pathophysilogical contribution of PAF on the pathogenesis of diabetic and cisplatin nephropathy was demonstrated in PAF receptor gene-targeted mouse, but, however, (4) significant co-relation between polymorphism of PAF acetylhydralase gene and pathogenesis and/or progression of diabetic nephropathy has not been shown so far.
These results will lead to new insight to the significances of lipid autacoids in the kidney.

Report

(3 results)
  • 1996 Annual Research Report   Final Research Report Summary
  • 1995 Annual Research Report
  • Research Products

    (38 results)

All Other

All Publications (38 results)

  • [Publications] 渡辺 毅,他: "Prostaglandin F_2 a stimulates formation of the p21^<ras>-GTP complex and mitogen-activated protein kinase activity in NIH-3T3 cells cia a Gq-protein-coupledpathway." J.Biol.Chem.270. 8984-8990 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] 浅野 健一郎,他: "Distribution of platelet-activating factor receptor mRNA along the ranephron segments." Biochem.Biophys.Res.Commun.225. 352-357 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] 浅野 健一郎,他: "Distribution of thromboxane A_2 receptor mRNA along the mouse nephron segments." Biochem.Biophys.Res.Commun.226. 613-617 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] 渡辺 毅,他: "Positive and negative regulation of cell proliferation through prostaglandin receptors in NIH-3T3 cells." J.Cell.Physiol.169. 401-409 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] 山田 秀臣,他: "Mechanism of [Ca^<2+>] increase by exracellular ATP in isolated rabbit renal proximal tubules." Am.J.Physiol.270. C1096-C1104 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] 山田 秀臣,他: "Roles of Ca^<2+> and PKC in the regulation of acid/base transport in isolated proximal tubules." Am.J.Physiol.271. F1068-F1076 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] H.Yi,M.Fukagawa,H.Yamato,M.Kumagai: "Prevention of enhanced parathyroid hormone secretion,synthesis and hyperplasia by mild dietary phosphorus restriction in rats with early chronic renal failure : possible direct role of phosphorus." Nephron. 70. 242-248 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] G.Seki,S Taniguchi,S.Uwatoko,K.Suzuki: "Activation of the basolateral Cl conductance by cAmp i rabbit renal proximal tubule S3 segments." Pflugers Arch. 430. 88-95 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] F.Takemoto,S.Uchida,H.Katagiri,Y.Oka: "Desensitization of endothelin-1 binding by vasopressin via a cAMP mediated pathway in rat CCD" Am.J.Physiol. 268. F385-390 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] H.Yamada,G.Seki,S.Taniguchi,S.Uwatoko: "Effect of concmycin on cell pH in isolated renal proximal tubules." Biochem.Biophys.Res Commun.225. 215-218 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] 黒川 清,他: "Effects of hormones on renal function" Textbook of Nephrology,Edited by S.G.Massry and R.J.Glassock,Williams & Wilkins, 172-181 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] 渡辺 毅,他: "腎とエイコサノイド,PAF" 治療学, 29,10,69-73 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] H.Yi, M.Fukagawa, H.Yamato, M.Kumagai, T.Watanabe and K.Kurokawa: "Prevention of enhanced parathyroid hormone secretion, synthesis and hyperplasia by mild dietary phosphorus restriction in rats with early chronic renal failure : possible direct role of phosphorus" Nephron. 70. 242-248 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] T.Watanabe, I.Waga, Z-i.Honda, K.Kurokawa, and T.Shimizu: "Prostaglandin F_2 alpha stimulates formation of the p21^<ras> -GTP complex and mitogen-activated protein kinase activity in NIH-3T3 cells via a Gq-protein-coupled pathway" J.Biol.Chem.270. 8984-8990 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] G.Seki, S.Taniguchi, S.Uwatoko, K.Suzuki and K.Kurokawa: "Activation of the basolateral C1^- conductance by cAMP in rabbit renal proximal tubule S3 segments" Pflugers Arch.430. 88-95 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] F.Takemoto, S.Uchida, H.Katagiri, Y.Oka, A.nakao and K.Kurokawa: "Desensitization of endothelin-1 binding by vasopressin via a cAMP-mediated pathway in rat CCD" Am.J.Physiol.268. F385-F390 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] K.Asano, S.Taniguchi, A.Nakao, T.Watanabe and K.Kurokawa: "Distribution of platelet-activating factor receptor mRNA along the rat nephron segments" Biochem.Biophys.Res.Commun.225. 352-357 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] K.Asano, S.Taniguchi, A.Nakao, T.Maruyama, T.Watanabe and K.Kurokawa: "Distribution of thromboxane A_2 receptor mRNA along the mouse nephron segments" Biochem.Biophys.Res.Commun.226. 613-617 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] H.Yamada, G.Seki, S.Taniguchi, S.Uwatoko, K.Suzuki and K.Kurokawa: "Mechanism of [Ca^<2+>] increase by exracellular ATP in isolated rabbit renal proximal tubules" Am. J.Physiol.270. C1096-C1104 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] H.Yamada, G.Seki, S.Taniguchi, S.Uwatoko, K.Suzuki and K.Kurokawa: "Effect of ionomycin on cell pH in isolated renal proximal tubules" Biochem.Biophys.Res.Commun.225. 215-218 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] H.Yamada, G.Seki, S.Taniguchi, S.Uwatoko, K.Suzuki and K.Kurokawa: "Roles of Ca^<2+> and PKC in the regulation of acid/base transport in isolated proximal tubules" Am.J.Physiol.271. F1068-F1076 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] N.Hashimoto, T.Watanabe, Y.Ikeda, H.Yamada, H.Mitsui, S.Taniguchi, and K.Kurokawa: "Prostaglandins induce cell proliferation of rat hepatocyte through an EP3 subtype prostagalndin E_2 receptor" Am.J.Physiol.(in press). (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] K.Kurokawa and S.Taniguchi: "Effects of hormones on renal function" Textbook of Nephrology, Edited b S.G.Massry and R.J.Glassock, Williams & Wilkins. 172-181 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] T.Watanabe: "Positive and negative regulation of cell proliferation through prostaglandin receptors in NIH-3T3 cells" J.Cell.Physiol.169. 401-409 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] 浅野 健一郎,他: "Distribution of platelet-activating factor receptor mRNA along the rat nephron segments." Biochem.Biophys.Res.Commun.225. 352-357 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] 浅野 健一郎,他: "Distribution of thromboxane A_2 receptor mRNA along the mouse nephron segments." Biochem.Biophys.Res.Commun.226. 613-617 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] 渡辺 毅,他: "Positive and negative regulation of cell proliferation through prostaglandin receptors in NIH-3T3 cells." J.Cell.Physiol.169. 401-409 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] 山田 秀臣,他: "Mechanism of [Ca^<2+>]_i increase by exracellular ATP in isolated rabbit renal proximal tubules." Am.J.Physiol.270. C1096-C1104 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] 山田 秀臣,他: "Roles of CA^<2+> and PKC in the regulation of acid/base transport in isolated proximal tubules." Am.J.Physiol.271. F1068-F1076 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] ザビ-ネ ノイゲバウアー,他: "Defective homocysteine metabolism as a risk factor for diabeticretinopathy." Lancet. (in press).

    • Related Report
      1996 Annual Research Report
  • [Publications] 黒川 清,他: "Effects of hormones on renal function." Textbook of Nephrology,Edited by S.G.Massry and R.J.Glassock,Williams & Wilkins, 172-181 (1995)

    • Related Report
      1996 Annual Research Report
  • [Publications] 谷口 茂夫,他: "Mechanism of aldosterone action." Principles of Medical Biology,Edited by E.E.Bittar,JAI Press INC(in press),

    • Related Report
      1996 Annual Research Report
  • [Publications] 渡辺毅 他: "Prostuglandin F2 alpha stimulates formation of p21ras-GTP complex and mitogen-activated protein kinase in NIH-3T3 cells via." J Bio Chem. 270. 8984-8990 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] 本田善一郎 他: "Gq pathway desensitizes chemotactic receptor-induced calcium signaling via inositol trisphosphate receptor down-regulation." J Bio Chem. 270. 4840-4844 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] 中尾彰秀 他: "Desensitization of endothelin-1 binding by vasopressin via a cAMP-mediated pathway in rat CCD." Am J Physiol. 268. F385-390 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] 谷口茂夫 他: "Stable measurements of intracellular calcium concentrations with Fura-2 in isolated rabbit renal proxial tubules." Cell Physiol Biochem. 5. 286-289 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] 谷口茂夫 他: "Activation of the basolateral CI conductance by cAMP in rabbit renal proximal tubule S3 segments." Pflugers Arch-Eur J Physiol. 430. 88-95 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] 橋本直明 他: "Prostanoid secretion by rat hepatic sinusoidal endothelial cells and its regulation by exogenous ATP." Hepatology. 21. 1713-1718 (1995)

    • Related Report
      1995 Annual Research Report

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Published: 1995-04-01   Modified: 2016-04-21  

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