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Clarification of pathophysiology and development of Gene therapy for inflammatory fibroproliferative arterial Disease

Research Project

Project/Area Number 09470170
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Circulatory organs internal medicine
Research InstitutionKYUSHU UNIVERSITY

Principal Investigator

UENO Hikaru  Kyushu Univ., Dept. of Cardiovasc Med., Assoc. Prof., 医学部, 講師 (50260378)

Co-Investigator(Kenkyū-buntansha) NISHIDA Takahiro  Kyushu Univ., Dept. of Cardiovasc Surg, Asssist. Prof., 医学部, 助手 (50284500)
OHHARA Yhuichi  Kyushu Univ., Dept. of Cardiovasc Med., Asssist. Prof., 医学部, 助手 (90185364)
TSUTSUI Hiroyuki  Kyushu Univ., Dept. of Cardiovasc Med., Asssist. Prof., 医学部, 助手 (70264017)
SUEISHI Katsuo  Kyushu Univ., Dept. of Pathol., Prof., 大学院・医学系研究科, 教授 (70108710)
MORI Eizou  Toukai Univ., Dept. of Med., Assoc. Prof., 医学部, 助教授 (90146598)
Project Period (FY) 1997 – 1999
Project Status Completed (Fiscal Year 1999)
Budget Amount *help
¥13,100,000 (Direct Cost: ¥13,100,000)
Fiscal Year 1999: ¥4,400,000 (Direct Cost: ¥4,400,000)
Fiscal Year 1998: ¥3,900,000 (Direct Cost: ¥3,900,000)
Fiscal Year 1997: ¥4,800,000 (Direct Cost: ¥4,800,000)
Keywordsgene transfer / adenovirus / mutated receptors / TGF-β / CNP / TEPI / D / N Ras / fibrosis / NFxB / 組換えアデノウイルス / 遺伝子治療 / 再狭窄 / 血管新生 / TGF-b / H-ras / FGF
Research Abstract

1. By adenovirus-mediated gene transfer of a dominant-negative H-ras, p21WAF1, C-type natriuretic peptide (CNP) or tissue factor pathway inhibitor (TFPI), significant inhibition of neointimal formation in injured articles was achieved in rats and rabbits. Using a needle catheter and an adnovirus expressing CNP, inhibition of neointimal hyperplasia can be attained in pig coronary articles.
2. Adenovirus-mediated in vivo TFPI gene transfer into an injured rabbit artery completely inhibits the recurrent thrombosis induced by shear stress even in the presence of catecholamine, without affecting systematic coagulation status. This method may have the potential the treatment of human thrombosis.
3. A truncated TGF-β type II receptor works as a dominant-negative receptor to suppress TGF-βsignaling. Introducing the truncated TGF-β receptor into livers of dimethylnitrosamine-treated rats markedly inhibited liver fibrosis and saved all rats, indicating that TGF-β does play a central role in fibrogenesis and that anti-TGF-β intervention could be therapeutically useful.
4. A soluble TGF-β receptor expressed in muscle effectively suppressed TGF-β signaling in a remote organ, liver as the truncated TGF-β receptor did. This strategy should facilitate clarification of the role of TGF-β (and other growth factors) in vivo in various organs where direct gene transfer seems to be difficult.

Report

(4 results)
  • 1999 Annual Research Report   Final Research Report Summary
  • 1998 Annual Research Report
  • 1997 Annual Research Report
  • Research Products

    (93 results)

All Other

All Publications (93 results)

  • [Publications] Honda M, et al: "Experimental subretinal neovascularization is inhibited by adenovirus0mediated soluble VEGF/flt-1 receptor gene transfection: A role of Vegf and possible treatment for SRN in age-related macular degeneration"Gene Therin press.. (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Sakamoto T, et al.: "Blockade of TGF-b by in vivogene transfer of a soluble TGF-b TYPE II receptor in the muscle inhibits corneal opacification, edema and angiogenesis."Lab. Invest. (in press). (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Tremain R, et al: "Defects in TGF-b signaling overcome senescence of mouse keratinocytes expressing v-H-ras."Oncogene. (in press). (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Uruno T, et al: "Distinct regulation of myoblast differentiation by intracellular and extracellular fibroblast growth factor-1"Growth Factors. 17. 93-113 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Glick A, et al.: "Defects in TGB-b signaling cooperate with a Ras oncogene to cause rapid aneuploidy and malignant transformation of mouse keratinocytes. Proc."Natl. Acad. Sci. 96. 14949-14954 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Eguchi S, et al.: "Intracellular signaling of angiotensin II-induced p7- S6 kinase phosphorylation at Ser 411 in vascular smooth muscle cells."J. Biol. Chem.. 274. 36843-36851 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Ueno H, et al: "Local expression of C-type natriuretic peptide markedly suppresses neointimal formation in rat injured arteries through an autocrine/paracrine loop."Circulation. 96. 2272-2279 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Ueno H, et al.: "Adenovirus-mediated transfer of a dominant-negative H-ras suppresses neointimal formation in balloon-injured arteries in vivo."Arterioscl. Thromb. Vasc. Biol.. 17. 898-904 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Takahashi T, et al: "Angiotensin II stimulates mitogen-activated protein kinases and protein synthesis by a Ras-independent pathway in vascular muscle cells."J. Biol. Chem. 272. 16018-16022 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Ueno H, et al.: "Adenovirus-mediated transfer of cyclin-dependent kinase inhibitor-p21 suppresses neointimal formation in the balloon-injured rat carotid arteries in viv."Ann. NY. Acad. Sci.. 811. 401-411 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Qi Z, et al: "Blockade of TGF-b signaling prevents liver fibrosis and dysfunction in the rat."Proc. Natl. Acad. Sci. USA. 96. 2221-2230 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Yukawa H, et al: "In vitro growth suppression of vascular smooth muscle cells using adenovirus-mediated gene transfer of a truncated form of fibroblast growth factor receptor."Atherosclerosis. 141. 125-132 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Li Q, et al: "Stretch-induced collagen synthesis in cultured smooth muscle cells from rabbit aortic media and a possible involvement of angiotensin II and transforming growth factor-b."Vas. Res.

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Maru Y et al: "Shibuya M. Virally activated Ras cooperates with integrin to induce tubulogenesis in sinusoidal endothelial cell lines"J. Cell. Physiol. 176. 223-234 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Li Q, et al: "Stretch-induced proliferation of cultured vascular smooth cells and a possible involvement of local renin-angiotensin system and platelet-derived growth factor."Hypertens. Res. 20. 217-223 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Ueno H et al.: "Adenovirus-mediated expression of secreted form of basic finbroblast growth factor (FGF-1) incuces cellular proliferation and angiogenesis in vivo."Arterioscl. Thromb. Vasc. Biol.. 17. 24532460 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Honda M., Sakamoto T., Ishibashi T., Inomata H., Ueno H.: "Experimental subretinal neocascularization is inhibited by adenovirus-mediated soluble VEGF/flt-1 receptor gene transfection: A role of VEGF and possible treatment for SRN in age-related macular degeneration"Gene ther. (in press). (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Sakamoto T., Ueno H., Sonoda KH., Shikizu K. Ohashi H., Inomata H.: "Blockade of TGF-β by in vivo gene transfer of a soluble TGF-βtype II receptor in the muscle inhibits corneal opacification, edema and angiogenesis"Lab. Invest.. (in press). (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Tremain R., Marko M., Kinnimulki V., Ueno H., Erwin Bottinger E., Glick A.: "Defects in TGF-β signaling overcome senescence of mouse keratinocytes expressing v-H-ras"Oncogene. (in press). (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Uruno T., Oki J., Ozawa K., Kiyakawa K., Ueno H., Imamura T.: "Distinct regulation of myoblast differentiation by intracellular and extracellular fibroblast growth factor-1"Growth Factors. 17. 93-113 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Glick A., Popescu N., Alexander V., Ueno H., Bottinger E., Yupsa SH.: "Defects in TGF-β signaling cooperate with a Ras oncogene to cause aneuploidy and malignant transformation of mouse keratinocytes"Porc. Natl. Acad. Sci. USA. 96. 14949-14954 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Eguchi S., Iwasaki H., Ueno H., Frank GD., Motley ED., Eguchi K., Marumo F., Hirata Y., Inagami T.: "Intracellular signaling of angiotensin II-induced p70 S6 kinase phosphorylation at Ser 411 in vascular smooth muscle cells"J. Biol. Chem.. 274. 36843-36851 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Saadeh PB., Mehrara BJ., Steinbreach DS., Dudziak ME., Greenwald JA., Luchs JS., Spector JA., Ueno H, Gittes GK., Longaker MT.: "Transforming growth factor beta 1 modulates the expression of VEGF by osteoblasts"Am. J. Physiol.. (in press). (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Steinbrech DS., Mehrara BJ., Steinbrech DS., Spector JA., Greenwald JA., Chin GS., Ueno H., Gittes GK., Longaker MT.: "Mechanisms of FGF-2 modulation of VEGF expression by osteoblasts"Endocrinology. (in press). (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Takayama K., Ueno H., Nakanishi Y., Sakamoto T., Inoue K., Matsuo M., Pei X-H, Shimizu K., Oohashi H., Hara N.: "Suppression of tumor angiogenesis and growth by gene transfer of a soluble form of VEGF receptor into a remote organ"Vancer Res.. (in press). (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Ueno H., Sakamoto T., Nakamura T., Atsuchi N., Takeshita A., Shimizu S., Ohashi H.: "A soluble TGF-β receptor expressed in muscle prevents liver fibrogenesis and dysfunction in rats"Hum. Gene Ther.. 11. 33-42 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Morishige K., Shimokawa H., Yamawaki T., Miyata K., Eto Y., Kandabashi T., Yogo K., Higo T., Egashira K., Ueno H., Takeshita AS.: "Local adenovirus-mediated transfer of C-type natriuretic peptide suppresses vascular remodeling in porcine coronary arteries in vivo"J. Am. Coll. Cardiol.. (in press). (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Kotani K., Ogawa W., Hino Y., Kitamura T., Ueno H., Sano W., Sutherland C., Granner DK., Kasuga M.: "Dominant-negative forms of Akt (protein kinase B) and atypical PKCo do not prevent insulin inhibition of PEPCK gene transcription"J. Biol. Chem.. 274. 21305-21312 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Iwasaki H., Eguchi S., Ueno H., Marumo F., Hirata Y.: "Endothelin-mediated vascular growth requires p42/p44 MAP kinase and p70 S6 kinase cascades via transactivation of epidermal growth factor receptor"Endocrinology. 140. 4659-4668 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Saiki M., Mita T., Takahashi J., Tani S., Yukawa H., Ueno H., Mikawa T., Itoh N., Kikuchi H., Hashimoto N., Miyatake S.: "Adenovirus-mediated gene transfer of a truncated form of fibroblast growth factor receptor inhibits growth of glioma cells both in vitro and in vivo"J. Neuro-Oncology. (in press). (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Nishida T., Ueno H., Atsuchi N., Kawano R., Takeshita A., Yasui H.: "Adenovirus-mediated local expression of human tissue factor pathway inhibitor eliminates shear stress-induced recurrent thrombosis in the injured carotid artery of the rabbit"Circ. Res.. 84. 1446-1452 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Matsumoto T., Yokote K., Tamura K., Takemoto M., Ueno H., Saito Y., Mori S.: "Platelet-derived growth factor activities p38 mitogen activated protein kinase through res-dependent pathway which is important for actin reorganization and cell migration"J. Biol. Chem.. 274. 13954-13960 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Yamamoto H., Atsuchi N., Tanaka H., Ogawa W., Abe M., Takeshita A., Ueno H.: "Roles of H-ras in signaling by TGF-β: H-ras is essential in activation of MAP kinase, partially involved in transcriptional activation by TGF-β but not in signaling of anti-proliferative response of TGF-β"Eur. J. Biochem.. 264. 110-119 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Takahashi T., Ueno H., Shibuya M.: "VEGF activates protein kinase C-dependent, but Ras-independent Raf-MEK-MAP kinase pathway for DNA synthesis in primary endothelial cells"Oncogene. 18. 2221-2230 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Qi Z., Atsuchi N., Ooshima A., Takeshita A., Ueno H.: "Blockade of TGF-β signaling prevents liver fibrosis and dysfunction in the rat"Proc. Natl. Acad. Sci. USA. 96. 2345-2349 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Yukawa H., Miyatake S., Saiki M., Takeshita J., Mima T., Ueno H., Nagata I., Kikuchi H., Hashimoto N.: "In vitro growth suppression of vascular smooth muscle cells using adenovirus-mediated gene transfer of a truncated form of fibroblast growth factor receptor"Atherosclerosis. 141. 125-132 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Maru Y., Yamaguchi S., Takahashi T., Ueno H., Shibuya M.: "Virally activated Ras cooperates with integrin to induce tubulogenesis in sinusoidal endothelial cell lines"J. Cell Physiol.. 176. 223-234 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Li Q., Marugaki Y., Ueno H., Ooshima A.: "Stretch-induced proliferation of cultured vascular smooth muscle cells and a possible involvement of local renin-angoitensin system and platelet-derived growth factor"Hypertens. Res.. 20. 217-223 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Ueno H., Li. J-J., Masuda S., Qi Z., Tamamoto H., Takeshita A.: "Adenovirus-mediated expression of secreted form of basis fibroblast growth factor (FGF-2) induces cellular proliferation and angiogenesis in vivo"Arteriosci. Thromb. Vasc. Biol.. 17. 2453-2460 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Ueno H., Haruno A., Morisaki N., Furuya M., Kangawa K., Takeshita A., Saito Y.: "Local expression of C-type natriuretic peptide markedly suppresses neointimal formation in rat injured arteries through an autocrine/patacrine loop"Circulation. 96. 2272-2279 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Ueno H., Yamamoto H., Ito S., Li J.-J., Takeshita A.: "Adenovirus-mediated transfer of a dominant-negative H-ras suppresses neuoitimal iformation n balloon-injured arteries in vivo"Arteriosci. Thromb. Vasc. Biol.. 17. 898-904 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Takahashi T., Kawahara Y., Okuda M., Ueno H., Yokoyama M.: "Angiotensin II stimulates mitogen-activated protein kinases and protein synthesis by a Ras-independent pathway in vascular smooth muscle cells"J. Biol. Chem.. 272. 16018-16022 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Ueno H., Masuda S., Li. J.-J., Nishio S., Li. J-J., Yamamoto H., Takeshita A.: "Adenovirus-mediated transfer of cyclin-dependent kinase inhibitor-p21 suppresses neuiontimal formation in the balloon-injured rat carotid arteries in vivo"Ann. NY. Acad. Sci.. 811. 401-411 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Li. Q. Muragaki Y, Hatamura I, Ueno H, Ooshima A: "Stretch-induced collagen synthesis in cultured smooth muscle cells from rabbi aortic media and a possible involvement of angiotensin II and transforming growth factor-β"Vas. Res.. 35. 93-103 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Honda M, et al: "Experimental subretinal neovascularization is inhibited by adenovirus-mediated soluble VEGF/flt-1 receptor gene transfection:A role of VEGF possible treatment for SRN in age-related macular degeneration."Gene Ther. (in press). (2000)

    • Related Report
      1999 Annual Research Report
  • [Publications] Sakamoto T, et al.: "Blockade of TGF-β by in vivo gene transfer of a soluble TGF-βtype II receptor in the muscle inhibits corneal opacification, edema and angiogenesis."Lab. Invest. (in press). (2000)

    • Related Report
      1999 Annual Research Report
  • [Publications] Tremain R, et al.: "Defectcts in TGF-β signaling overcome senescence of mouse keratinocytes expressing v-H-ras."Oncogene. (in press). (2000)

    • Related Report
      1999 Annual Research Report
  • [Publications] Uruno T, et al.: "Distinct regulation of myoblast defferentiation by intracellular and extracellular fibroblrast growth factor-1."Growth Factors. 17. 93-113 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Glick A, et al.: "Defects in TGF-βsignaling cooperate with a Ras oncogene to cause rapid aneuploidy and malignant transformation of mouse keratinocytes. Proc."Natl. Acad. Sci. 96. 14949-14954 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Eguchi S. et al.: "Intracellular signaling of angiotensin II-induced p70 S6 kinase phosphorylation at Ser 411 in vascular smooth muscle cells."J. Biol. Chem.. 274. 36843-36851 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Saadeh PB, et al.: "Transforming growth factor beta 1 modulates the expression of VEGF by osteoblasts."Am. J. Physiol.. (in press). (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Steinbrech DS, et al.: "Mechanisms of FGF-2 modulation of VEGF expression by osteoblasts."Endocrinology. (in press). (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Takayama K, et al.: "Suppression of tumor angiogeesis and growth by gene transfer of a soluble form of VEGF receptor into a remote organ."Cancer Res.. (in press). (2000)

    • Related Report
      1999 Annual Research Report
  • [Publications] Ueno H, et al.: "A soluble TGF-β receptor expressed in muscle prevents liver fibrogenesis and dysfunction in rats."Hum Gene Ther.. 11. 33-42 (2000)

    • Related Report
      1999 Annual Research Report
  • [Publications] Morishige K, et al.: "Takeshita A. Local adnovirus-mediated transfer of C-type natriuetic peptide suppresses vascular remodeling in porcine coronary arteries in vivo."J. Am. Coll. Cardiol.. (in press). (2000)

    • Related Report
      1999 Annual Research Report
  • [Publications] Kotani K, et al.: "Dominant-negative forms of Akt(protein kinase B) and atypicak PKCδ do not prevent insulin inhibition of PEPCK gene transcription."J. Biol. Chem.. 274. 21305-21312 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Iwasaki H, et al.: "Endothelin-mediated bascular growth requires p42/p44 MAP kinase and p70 S6 kinase cascades via transactivation of epidermal growth factor receptor."Endocrinology. 140. 4659-4668 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Saiki M, et al.: "Adenovirus-mediated gene transfer of a truncated form of fibroblast growth factor receptor inhibits growth of glioma cells both in vitro and in vivo."J. Neuro-Oncology. (in press). (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Nishida T, et al.: "Adenovirus-mediated local expression of human tissue factor pathway inhibitor eliminates shear stress-induced recurrent thrombosis in the injured carotid artery of the rabbit."Circ Res. 84. 1446-1452 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Matsumoto T, et al.: "Plantelet-derived growth factor activates p38 mitogen activated protein kinase through ras- dependent pathway which is important for actin reorganization and cell migration."J. Biol Chem. 274. 13954-13960 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Yamamoto H, et al.: "Roles of H-ras in signaling by TGF-β:H-ras is essential in activation of MAP kinase, partially involved in transcriptional activation by TGF-β but not in signaling of anti-proliferative response of TGF-β."Eur. J. Biochem. 264. 110-119 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Takahashi T, et al.: "VEGF activates protein kinase C-dependent, but Ras-independent Raf-MEK-MAP kinase pathway fro DNA synthesis in primary endothelial cells."Oncogene. 18. 2221-2230 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Qi Z, et al.: "Blockad of TGF-β signaling prevents liver fibrosis and dysfunction in the rat."Proc. Natl. Acad. Sci. USA. 96. 2221-2230 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Yukawa H, et al.: "In vitro growth suppression of vascular smooth muscle cells using adenovirus-mediated gene transfer of a truncated form of fibroblast growth factor receptor."Atherosclerosis. 141. 125-132 (1998)

    • Related Report
      1999 Annual Research Report
  • [Publications] Li Q et al.: "Stretch-induced collagen synthesis in culturede smooth muscle cells from rabbit aortic media and a possible involvement of angiotensis II and transforming growth factor-β."Vas. Res. 35. 93-103 (1998)

    • Related Report
      1999 Annual Research Report
  • [Publications] Maru Y, et al.: "Shibuya M. Virally activated Ras cooperates with integrin to induce tubulogenesis in sinusoidal endothelial cell lines"J. Cell. Physiol. 176. 223-234 (1998)

    • Related Report
      1999 Annual Research Report
  • [Publications] Li Q et al.: "Stretch-induced proliferation of cultured vascular smooth muscle cells and a possible involvement of local renin-angiotensis system and platelet-derived grwoth factor."Hypertens. Res. 20. 217-223 (1997)

    • Related Report
      1999 Annual Research Report
  • [Publications] Ueno H, et al.: "Adeovirus-mediated expression of secreted form of basic fibroblast growth factor(FGF-2) induces cellular proliferation and angiogenesis in vivo."Arterioscl. Thromb. Vasc, Biol.. 17. 2453-2460 (1997)

    • Related Report
      1999 Annual Research Report
  • [Publications] Ueno H, et al.: "Local expressison of C-type natriuretic peptide markedly suppresses neointimal formation in rat injured arteries through an autocrine/paracrine loop."Circulation. 96. 2272-2279 (1997)

    • Related Report
      1999 Annual Research Report
  • [Publications] Ueno H, et al.: "Adenovirus-mediated transfer of a dominant-negative H-ras suppresses neointimal formation in balloon-injured arteries in vivo."Arterioscl. Thromb. Vasc, Biol.. 17. 898-904 (1997)

    • Related Report
      1999 Annual Research Report
  • [Publications] Takahashi T, et al.: "Angiotensin II stimulates mitogen-activated protein syntesis by a Ras-independent pathway in vascular smooth muscle sells."J. Biol. Chem.. 272. 16018-16022 (1997)

    • Related Report
      1999 Annual Research Report
  • [Publications] Ueno H, et al.: "Adenovirus-mediated transfer of cyclin-dependent kinase inhibitor-p21 suppresses neointimal formation in the balloon-injured rat carotid arteries in vivo."Ann. NY. Acad. Sci.. 811. 40-411 (1997)

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  • [Publications] Matsumoto T,et al.: "Pletelet-berived growth factor activates p38 mitogen activated protein kinase through ras-dependent pathway shiech is important for actin reorganization and cell miaration." Journal of Biological Chemistry. (in press).

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  • [Publications] Qi Z,et al.: "Blockade of TGF-β signaling prevents liver fibrosis and dysfunction." Proc.Natl.Acad.Sci.USA.(in press).

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  • [Publications] Yamamoto H,et al.: "Roles of H-ras in signaling by TGF-β:H-ras is essential in activation of MAP kinase,partially involved in transcriptional activation by TGF-β but not in sinaling ofanti-proliferative response of TGF-β" Eur.J.Biochem.(in press).

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  • [Publications] Ohashi M,et al.: "Adenovirus-mediated p53 tumor suppressor gene therapy of human gastric cancer cells in vitro and in vivo." Gut. (in press).

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  • [Publications] Yukawa H,et al.: "In vitro growth suppression of vascular smooth muscle cells using adenovirus-mediated gene transfer of a truncated from of fibroblast growth factor receptor." Atherosclerosis. (in press).

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  • [Publications] Sakamoto T,et al.: "Trsnsfection of LacZ gene to retina by an adenoveral vector causes retinal dysfunction with no apparent morphological changes." Hum.Gene Ther.9. 789-799 (1998)

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  • [Publications] Takayama K,et al.: "The levels of integrin α V and β5 maywell predict the susceptibility to adenovinus-mediated gene transfer in human lung cancer cells." Gene Ther.5. 361-368 (1998)

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  • [Publications] Sakamoto T,et al.: "A vitrctomy improves the transfection efficiency of adenoviral vector-mekiated gene transfer to Muller cells." Gene Ther.5. 1088-1097 (1998)

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  • [Publications] LiQ,et al.: "Stretch-induced collagen synthesis in cultured smooth muscle cells from rabbit aortic media and possible involvment of angiotensin「 and TGFβ" J.Vasc.Res.35. 93-103 (1998)

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  • [Publications] Maru Y,et al.: "Virally activated Ras cooperates wit integrin to induce tubulogenesis in sinusoidal endothelial cell lines." J.Cell.Physiol.176. 223-234 (1998)

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  • [Publications] Sakamoto T.,et al.: "Transfection of LacZ gene to retina by an adenoviral vector causes retinal dysfunction with no apparent morphological changes." Hum.Gene Ther.(in press).

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  • [Publications] Takayama K.,et al: "The levels of integrin aV and b5 may well predict the susceptibility to adenovirus-mediated gene transfer in human lung cancer cells." Gene Ther.(in press).

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  • [Publications] Li Q.,et al.: "Stretch-induced collagen syntesis in cultured smooth muscle cells from rabbit aortic media and possible involvement of angiotensin II and TGF-b." Vasc.Res.(in press).

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  • [Publications] Ueno H.,et al.: "Adenovirus-mediated expression of secreted form of basic fibroblast growth factor(FGF-2)induces cellular proliferation and angiogenesis in vivo." Arterioscl.Thromb.Vasc.Biol.17. 2453-2460 (1997)

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  • [Publications] Ueno H.,et al.: "Adenovirus-mediated transfer of a dominant-negative H-ras suppresses neointimal formation in balloon-injured arteries in vivo.Arterioscl." Thromb.Vasc.Biol.17. 898-904 (1997)

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  • [Publications] Ueno H.,et al: "Local expression of C-type natriuretic peptide markedly suppresses neointimal formation in rat injured arteries through an autocrine/paracrine loop." Circulation. 96. 2272-2279 (1997)

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  • [Publications] Ueno H.,et al: "Adenovirus-mediated transfer of cyclin-dependent kinase inhibitor-p21 suppresses neointimal hyperplasia in balloon-injured arteries in vivo." Ann.NY Acad.Sci.811. 401-411 (1997)

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  • [Publications] Takahashi T.,et al.: "Angiotensin II stimulates mitogen-activated protein kinases ans protein synthesis by a rasindependent pathway in vascular smooth muscle cells." J.Biol.Chem.272. 16018-16022 (1997)

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  • [Publications] Kitamura Y.,et al.: "Interaction of Nck-associated protein 1 with activatied GTP-binding protein" Rac.Biochem.J.3332. 873-878 (1997)

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  • [Publications] Sakaue H.,et al.: "Phosphoinositide 3-kinase is required for insulin-induced but not for growth hormone-or hyperosmolarity-induced glucose uptake in 3T3-L1 adipocytes." Mol.Endocrinol.11. 1551-1562 (1997)

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  • [Publications] Li Q.,et al.: "Stretch-induced proliferation of cultured vascular smooth muscle cells and possible involvement of local renin-angiotensin system and platelet-derived growth factor." Hypertens.Res.20. 217-223 (1997)

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Published: 1997-04-01   Modified: 2016-04-21  

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