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1997 Fiscal Year Final Research Report Summary

Analysis of the effects of Gla-containing proteins and their receptors on the proliferation of vascular smooth muscle cells.

Research Project

Project/Area Number 08671240
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Hematology
Research InstitutionKYUSHU UNIVERSITY

Principal Investigator

TSUDA Hiroko  Kyushu Univ., Faculty of Medicine, Assistant Professor, 医学部, 講師 (30180003)

Co-Investigator(Kenkyū-buntansha) SHIMOKAWA Hiroaki  Kyushu Univ., Faculty of Medicine、Associate Professor, 医学部, 助教授 (00235681)
MIZUNO Kensaku  Kyushu Univ., Faculty of Biology, Associate professor, 理学部, 助教授 (70128396)
Project Period (FY) 1996 – 1997
KeywordsProtein S / Gas6 / Receptor tyrosine kinase / Vascular smooth muscle cells
Research Abstract

Novel receptor tyrosine kinases including Sky, which we have cloned from a Hep G2 cDNA library, Axl/Ufo and Mer/Eyk form a subfamily based on a unique extracellular domain. Recently gamma-carboxyglutamic acid (Gla)-containing proteins, protein S and Gas6, have been reported to be physiological ligands for the Axl/Sky subfamily of receptor tyrosine kinases. In this study, we tried to elucidate the physiological importance of the novel signaling pathway mediated by this ligand-receptor system in the proliferation of vascular smooth muscle cells.
Both human protein S and rat Gas6 failed to induce proliferation of rat arterial vascular smooth muscle cells, however, rat Gas6 potentiated the mitogenic activity of thrombin as reported by Nakano et al. Species specificity has been reported to exist in the interaction between protein S or Gas6 and Axl/Sky receptor subfamily, we are now analyzing the effect of human protein S on the proliferation of bovine and human vascular smooth muscle cells.
Analysis of the binding ability of the soluble receptors of human Axl, human Sky and mouse Mer composed of the extracellular domain of receptors fused to the Fc domain of immunoglobulin G1 showed that rat Gas6, but not human protein S,bound to Axl, Sky and Mer. The C-terminal sex hormone-binding globulin-like domain of Gas6 was indispensable for the binding of Gas6 to Axl and the N-terminal Gla domain had a regulatory role on the interaction.
We developed a swine model of coronary spasms with intimal thickening by chronically treating the outside of the coronary arteries with a inflammatory cytokine, IL-1beta. In order to know whether the novel signaling pathway mediated by binding protein S and Gas6 to Axl/Sky receptor family is implicated in formation of the vasospastic lesions, we proceed to determine the expression of these molecules in the lesions with proliferation of vascular smooth muscle cells.

  • Research Products

    (22 results)

All Other

All Publications (22 results)

  • [Publications] Iwasaka, M.: "Measurement of clottability of fibrin polymers using magnetic orientation." J.Appl.Phys.79. 4708-4710 (1996)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Tsuda, H.: "Thrombophilia found in patients with moyamoya disease." Clin. Neurol.Neurosurg.99 Suppl2. 229-233 (1997)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 岩坂 正和: "血栓線維素溶解系への磁場効果" 電気学会論文誌. 116-C. 163-169 (1996)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 津田 博子: "検査部における病態解析への模索:血栓性素因の病態解析" 臨床病理. 45. 1025-1030 (1997)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Nagata, K.: "Identification of the product of growth arrest-specific gene 6 as a common ligand for Axl,Sky,and Mer recepotor tyrosine kinases." J.Biol.Chem.271. 30022-30027 (1996)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Tanbae, K.: "Roles of γ-carboxylation and a sex hormone-binding globulin-likedomain in receptor-binding and in biological activities of Gas6." FEBS Letters.408. 306-310 (1997)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Nakno, T.: "Cell adhesion to phosphatidylserine mediated by a product of growth arrest-specific gene6." J.Biol.Chem.272. 29411-29414 (1997)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Shimokawa, H.: "Chronic treatment with interleukin-1β induces coronary intimal lesions and asospastic responses in pigs in vivo:The role of platelet-derived growth factor." J.Clin.Invest.97. 769-776 (1996)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Kozai, T.: "Platelet activating factor causes hyperconstriction at the inflammatory coronary lesions in pigs in vivo." Coron.Artery Dis.8. 423-432 (1997)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Fukumoto, Y.: "Vasculoprotective role of inducible nitric oxide synthase at inflammatory coronary lesion inducedby chronic treatment with interleukin-1β in pigs in vivo." Circulation. 96. 3104-3111 (1997)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Katsumata, N.: "Enhanced myosin light chain phophorylations as a central mechanism for coronaty artery spasm in a Swine model with interleukin-1β." Circulation. 96. 4357-4363 (1997)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Iwasaka, M.: "measurement of clottability of fibrin polymers using magnetic orientation." J.Appl.Phys.79. 4708-4710 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Tsuda, H.: "Thrombophilia found in patients with moyamoya disease." Clin.Neurol.Neurosurg.99 Suppl.2. S229-S233 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Iwasaka, M.: "Effect of magnetic field on fibrinolytic process. (in Japanese)" Trans.IEE of Japan. 116-C. 163-169 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Tsuda, H.: "Etiological analysis of thrombophilia. (in Japanese)" Jpn.J.Clin.Pathol.45. 1025-1030 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Nagata, K.: "Identification of the product of growth arrest-specific gene 6 as a common ligand for Axl, Sky, and Mer receptor tyrosine kinases." J.Biol.Chem.271. 30022-30027 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Tanabe, K.: "Roles of gamma-carboxylation and a sex hormone-binding globulin-like domain in receptor-binding and in biological activities of Gas 6." FEBS Letters. 408. 306-310 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Nakano, T.: "Cell adhesion to phosphatidylserine medhiated by a product of growth arrest-specific gene 6." J.Biol.Chem.272. 29411-29414 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Shimokawa, H.: "Chronic treatment with interleukin-1beta induces coronary intimal lesions and vasospastic responses in pigs in vivo : The role of platelet-derived growth factor." J.Clin.Invest.97. 769-776 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Kozai, T.: "Platelet activating factor causes hyperconstriction at the inflammatory coronary lesions in pigs in vivo." Coron.Artery Dis.8. 423-432 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Fukumoto, Y.: "Vasculoprotective role of inducible nitric oxide synthase at inflammatory coronary lesions induced by chronic treatment with interleukin-1b in pigs in vivo." Circulation. 96. 3104-3111 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Katusumata, N.: "Enhanced myosin light chain phophorylations as a central mechanism for coronary artery spasm in swine model with interleukin-1beta." Circulation. 96. 4357-4363 (1997)

    • Description
      「研究成果報告書概要(欧文)」より

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Published: 1999-03-16  

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