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Cloning of shear stress-sensitive endothelial genes

Research Project

Project/Area Number 08408039
Research Category

Grant-in-Aid for Scientific Research (A)

Allocation TypeSingle-year Grants
Section一般
Research Field Biomedical engineering/Biological material science
Research InstitutionThe University of Tokyo

Principal Investigator

ANDO Joji  Dept.of Biomedical Engineering, Graduate School of Medicine, The University of Tokyo, Associate Professor, 大学院・医学系研究科, 助教授 (20159528)

Co-Investigator(Kenkyū-buntansha) KAMIYA Akira  Dept.of Biomedical Engineering, Graduate School of Medicine, The University of T, 大学院・医学系研究科, 教授 (50014072)
Project Period (FY) 1996 – 1998
Project Status Completed (Fiscal Year 1998)
Budget Amount *help
¥21,500,000 (Direct Cost: ¥21,500,000)
Fiscal Year 1998: ¥1,900,000 (Direct Cost: ¥1,900,000)
Fiscal Year 1997: ¥2,000,000 (Direct Cost: ¥2,000,000)
Fiscal Year 1996: ¥17,600,000 (Direct Cost: ¥17,600,000)
Keywordsshear stress / endothelial cell / mRNA / differential display / G-protein / gene / 内皮細胞 / 壁ずり応力 / 血行力学因子
Research Abstract

The purpose of this study was to investigate endothelial gene which were responsive to shear stress generated by blood flow and to find genes encoding new bio-active substances. First, in order to evaluate whole number of shear stress-responsive genes in endothelial cells, differential display of mRNAs was performed. The results showed that 33 of 15O7mRNAs detected were up-regulated by a shear stress of 15 dynes/cm^2 for 6 h, while 27 were down-regulated, indicating that around 4% of the whole endothelial genes are shear-sensitive. Second, 16 genes were cloned from these 60 shear-sensitive genes and sequenced. Homology search revealed 6 known genes encoding laminin B1 chain, H^+-ATP synthase coupling factor 6, lysyl oxidase, myosin light chain kinase, NADH dehydrogenase, and interleukin-8 receptor and 10 unknown genes. Lastly, we constructed a cDNA library from human umbilical vein endothelial cells which had been exposed to a shear stress of 15 dynes/cm^2 for 8 h, and looked for new G-protein coupled receptors. As a result we obtained a new one which we named PEG-1 (Flow-induced Endothelial G-protein-coupled receptor. The receptor consists of 375 amino acids and has a homology to angiotensin receptors or chemokine receptors.

Report

(4 results)
  • 1998 Annual Research Report   Final Research Report Summary
  • 1997 Annual Research Report
  • 1996 Annual Research Report
  • Research Products

    (42 results)

All Other

All Publications (42 results)

  • [Publications] M.Nagase: "Genomic organization and regulation of expression of the lectin-like oxidized low-density lipoprotein receptor (LOX-1) gene." J.Biol.Chem.273. 33702-33707 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] T.Murase: "Fluid shear stress transcriptionally induces lectin-like oxidized LDL receptor-1 in vascular endothelial cells." Circ.Res.83. 328-333 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] M.Isshiki: "Endothelial Ca^<2+> waves preferentially originate at specific loci in caveolin-rich cell edges." Proc.Natl.Acad.Sci.U.S.A.95. 5009-5014 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] H.Watanabe: "An essential role of myosin light-chain kinase in the regulation of agonist-and fluid-flow-stimulated Ca^<2+> influx in endothelial cells." FASEB J. 12. 341-348 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] K.Kosaki: "Fluid shear stress increases the production of granulocyte-macrophage colony-stimulating factor by endothelial cells via mRNA stabilization." Circ.Res.81. 794-803 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] K.Masatugu: "Physiologic shear stress suppresses endothelin-converting enzyme-1 expression in vascular endothelial cells." J.Cardiovasc.Pharmacol.31. S42-S45 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] J.Ando: "Flow-induced endothelial gene regulation.In “Mechanical Forces and the Endothelium"" P.I.Lelkes ed.,Harwood Academic Publishers,London (in press), (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] A.Kamiya: "Responses of vascular endothelial cells to fluid shear stress : Mechanism.In “Biomechanics-Functional Adaptation and Remodeling"" K.Hayashi et al.eds.,Springer-Verlag,Tokyo, 28 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] M.Nagase, J.Abe, K.Takahashi, J.Ando, S.Hirose, and T.Fujita: "Genomic organization and regulation of expression of the lectin-like oxidized low-density lipoprotein receptor (LOX-1) gene." J.Biol.Chem.273. 33702-33707 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] K.Nakai, I.Sakuma, T.Ohta, J.Ando, A.Kitabatake, Y.Nakazato, and T.Takahashi: "Permeability characteristics of hemoglobin derivatives across cultured endothelial cell monolayers." J.Lab.Clin.Med.132. 313-319 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] T.Murase, N.Kume, R.Korenaga, J.Ando, T.Sawamura, T.Masaki, and T.Kita: "Fluid shear stress transcriptionally induces lectin-like oxidized LDL receptor-1 in vascular endothelial cells." Circ.Res.83. 328-333 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] M,Isshiki, J.Ando, R.Korenaga, H.Kogo, T.Fujimoto, T.Fujita, and A.Kamiya: "Endothelial Ca^<2+> waves preferentially originate at specific loci in caveolin-rich cell edges." Proc.Natl.Acad.Sci.U.S.A. 95. 5009-5014 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] H.Watanabe, R.Takahashi, X-X.Zhang.Y.Goto, H.Hayashi, J.Ando, M.Isshiki, M.Seto, H.Hidaka, I.Niki, and R.Ohno: "An essential role of myosin light-chain kinase in the regulation of agonist-and fluid-flow-stimurated Ca^<2+> influx in endothelial cells." FASEB J. 12. 341-348 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] K.Kosaki, J.Ando, R.Korenaga, T.Kurokawa, and A.Kamiya: "Fluid shear stress increase the production of granulocyte-macrophage colony-stimulating factor by endothelial cells via mRNA stabilization." Circ.Res.81. 794-803 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Y.Takada, C.Kato, S.Kondo, R.Korenaga, and J.Ando: "Cloning of cDNAs encoding G protein-coupled receptor expressed in human endothelial cells exposed to fluid shear stress." Biochem.Biophys.Res.Commun.240. 737-741 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] R.Korenaga, J.Ando, K.Kosaki, M.Isshiki, Y.Takada, and A.Kamiya: "Negative transcriptional regulation of the VCAM-1 gene by fluid shear stress in murine endothelial cells." Am.J.Physiol.273. C1506-C1515 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] T.Chun, H.Itoh, Y.Ogawa, N.Tamura, K.Takaya, T.Igaki, J.Yamashita, K.Doi, M.Inoue, K.Masatsugu, R.Korenaga, J.Ando, and K.Nakano: "Shear stress augments expressin of C-type natriuretic peptide and adrenomedulin." Hypertension. 29. 1296-1302 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] J.Ando, H.Tsuboi, R.Korenaga, K.Takahashi, K.Kosaki, M.Isshiki, T.Tojo, Y.Takada, and A.Kamiya: "Differential display and cloning of shear stress-responsive messenger RNAs in human endothelial cells." Biochem.Biophys.Res.Commun.225. 347-351 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Y.Wang, W.S.Shin, H.Kawaguchi, M.Inukai, M.Kato, A.Sakamoto, Y.Uehara, M.Miyamoto, N.Shimamoto, R.Korenaga, J.Ando, and T.Toyo-oka: "Contribution of sustained Ca^<2+> elevation for nitric oxide production in endothelial cells and subsequent modulation of Ca^<2+> transient in vascular smooth muscle cells in coculture." J.Biol.Chem.271. 5647-5655 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] M.Nagase: "Genomic organization and regulation of expression of the lectin-like oxidized low-density lipoprotein receptor (LOX-1) gene." J.Biol.Chem.273. 33702-33707 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] T.Murase: "Fluid shear stress transcriptionally induces lectin-like oxidized LDL receptor-1 in vascular endothelial cells." Circ.Res.83. 328-333 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] M.Isshiki: "Endothelial Ca^<2+> waves preferentially originate at specific loci in caveolin-rich cell edges." Proc.Natl.Acad.Sci.U.S.A.95. 5009-5014 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] H.Watanabe: "An essential role of myosin light-chain kinase in the regulation of agonist-and fluid-flow-stimulated Ca^<2+> influx in endothelial cells." FASEB J. 12. 341-348 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] K.Kosaki: "Fluid shear stress increases the production of granulocyte-macrophage colonystimulating factor by endothelial cells via mRNA stabilization." Circ.Res.81. 794-803 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] K.Masatugu: "Physiologic shear stress suppresses endothelin-converting enzyme-1 expression in vascular endothelial cells." J.Cardiovasc. Pharmacol.31. S42-S45 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] J.Ando: "Flow-induced endothelial gene regulation. In “Mechanical Forces and the Endothelium" (in press)" P.I.Lelkes ed.,Harwood Academic Publishers, London, (1999)

    • Related Report
      1998 Annual Research Report
  • [Publications] M.Isshiki: "Endothelial Ca^<2+> waves preferentially originate at specific loci in caveolin-rich cell edges." Proc.Natl.Acad.Sci.U.S.A.(in press).

    • Related Report
      1997 Annual Research Report
  • [Publications] K.KosaKi: "Fluid shear stress increases the production of granulocyte-macrophage colony-stimulating factor by endothelial cells via mRNA stabilization." Circ.Res.(in press).

    • Related Report
      1997 Annual Research Report
  • [Publications] H.Watanabe: "An essential role of myosin light-chain kinasein the regulation of agonist-and fluid-flow-stimulated Ca^<2+> influx in endothelial cells." FASEB J. (in press).

    • Related Report
      1997 Annual Research Report
  • [Publications] Y.Takada: "Cloning of cDNAs encoding G protein-coupled receptor expressed in human endothelial cells exposed to fluid shear stress." Biochem.Biophys.Res.Commun.240. 737-741 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] R.Korenaga: "Negative transcriptional regulation of the VCAM-1 gene by fluid shear stress in murine endothelial cells." Am.J.Physiol.273. C1506-C1515 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] T.Chum: "Shear stress augments expression of C-type natriuretic peptide and adrenomedulin." Hypertension. 29. 1296-1302 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] M.Miyasaka: "Involvement of selectins in atherogenesis : A primary or secondary event? Atherosclerosis IV : Recent Advances in Atherosclerosis Research" New York Academy of Sciences, 10 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] A.Kamiya: "Responses of vascular endothelial cells to fluid Shear stress : Mechanism. In "Biomechanics-Functional Adaptation and Remodeling"" Springer-Verlag,Tokyo, 27 (1996)

    • Related Report
      1997 Annual Research Report
  • [Publications] J.Ando: "Differential display and cloning of shear stress-responsive messenger RNAs in human endothelial cells." Biochem.Boiphys.Res.Commun.225. 347-351 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Y.Wang: "Contribution of sustained Ca^<2+> elevation for nitric oxide production in endothelial cells and subsequent modulation of Ca2+ transient in vascular smooth muscle cells in coculture." J.Biol.Chem.271. 5647-5655 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] H.Tsuboi: "Flow stimulates ICAM-1 expression time-and shear stress-dependently in human endothelial cells." Biochem.Boiphys.Res.Commun.206. 988-996 (1995)

    • Related Report
      1996 Annual Research Report
  • [Publications] Y.Takada: "Fluid shear stress increases the expression of thrombomodulin by cultured human endothelial cells." Biochem.Biophys.Res.Commun.205. 1345-1352 (1994)

    • Related Report
      1996 Annual Research Report
  • [Publications] W.Yang: "Exogenous nitric oxide inhibits proliferation of cultured vascular endothelial cells." Biochem.Biophys.Res.Commun.203. 1160-1167 (1994)

    • Related Report
      1996 Annual Research Report
  • [Publications] J.Ando: "Shear stress inhibits the adhesion of cultured mouse endothelial cells to lymphocytes by down-regulating VCAM-1 expression." Am.J.Physiol.267. C679-C687 (1994)

    • Related Report
      1996 Annual Research Report
  • [Publications] J.Ando: "Fluid shear stress differentialy modulates adhesion molecule expression in human vascular endothelial cells.In“Organ Microcirculation:Bridging between Basic and Clinical Sciences",M.Tshuchiya et al.eds.," Excerpta Medica,Tokyo, 8 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] J.Ando: "Flow-dependent regulation of gene expression in vascular endothelial cells." Jpn.Heart J., 14 (1996)

    • Related Report
      1996 Annual Research Report

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Published: 1996-04-01   Modified: 2016-04-21  

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