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2003 Fiscal Year Final Research Report Summary

Analysis of the Beta2-chimaerin signaling in phenotypiC modulation of vascular smooth muscle cells

Research Project

Project/Area Number 13832007
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field 細胞生物学
Research InstitutionKurume University

Principal Investigator

KATO Seiya  Kurume University School of Medicine, Department of Pathology, Associate Professor, 医学部, 助教授 (60268844)

Co-Investigator(Kenkyū-buntansha) FUJII Teruhiko  Kurume University School of Medicine, Department of Surgery, Assistant Professor, 医学部, 講師 (50199288)
Project Period (FY) 2001 – 2003
Keywordssmooth muscle, vascular / beta2-chimaerin / protein kinase C / phenotypes / atherosclerosis
Research Abstract

Phenotypic change of vascular smooth muscle cells (SMC) is an important aspect of atherogenesis. Activated cytokinegrowth factor network in the injured vessels subsequently induces a number of intracellular events resulting in the phenotypic modulation of SMC. Here, we investigated the role of beta2-chimaerin, a novel phorbol ester receptor with Rac GTPase-activating protein activity, in growth factor-stimulated SMC. Endogenous expression of beta2-chimaerin was detected in cultured human SMC by RT-PCR and immunohistochemistiy. Next, an overexpression of HA-tagged wild type human beta2-chimaerin was attempted in cultured rat SMC with a recombinant adenovirus (Adv-Ch). Confocal microscopy revealed 12-O-tetradecanoyl phorbol 13-acetate (TPA)-induced translocation of exogenous beta2-chimaerin from cytoplasm to plasma membrane in the presence of the PKC inhibitor (GF109203X). Proliferation of SMC stimulated by 10% FCS, bFGF (25ng/ml), and PDGF (10ng/ml) were inhibited by the infection with Adv-Ch (10-200MOI), but not with control viruses (Adv-LacZ), which was measured by cell counting and BrdU incorporation assays. PDGF-induced SMC migration was inhibited by the infection with Adv-Ch (200MOI) by about 25% in a modified Boyden chamber assay with the fibronectin-coated membrane. These data suggested that beta2-chimaerin might regulate proliferation and migration of SMC at the down-stream of the receptor tyrosine kinases. Beta2-chimaerin system may be involved in human atherogenesis, as is a potential therapeutic target.

  • Research Products

    (40 results)

All Other

All Publications (40 results)

  • [Publications] Fujii T, Kato S, Yamana H, Tanaka Y, Fujita H, Shirouzu K, Morimatsu M.: "Expression of G1 cell cycle markers and the effect of adenovirus-mediated overexpression of p21Waf-1 in squamous cell carcinoma of the esophagus"Int J Oncol.. 18. 157-163 (2001)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Shibata R, Kai, H Seki Y, Kato S, Morimatsu M, Kaibuchi K, Imaizumi T.: "Role of Rho-associated protein kinase in neointima formation after vascular injury."Circulation. 103. 284-289 (2001)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Zemmyo N, Komiya S, Hamada T, Hiraoka K, Kato S, Fujii T, Yano H, Irie K, Nagata K.: "Transcriptional activation of p21 by vitamine D3 vitamine K2 lead to differentiation of p53-deficient MG-63 osteosarcoma cells."Hum Pathol. 32. 410-416 (2001)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Hamada T, Yoshida T, Kinjo I, Minoguchi S, Yasukawa H, Kato S, Mimata H, Nomura Y, Seki Y, Kubo M, Yoshimura A.: "A mutant form of JAB/SOCS1 auguments the cytokine-induced JAK/STAT pathway by accelerating degradation of wild-type JAB/CIS family protein through the SOCS-box."J Biol Chem. 276. 40746-40754 (2001)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Wada Y, Kato S, Okamoto K, Izumaru S, Aoyagi S, Morimatsu M.: "Diltiazem, a calcium antagonist, inhibits matrix metalloproteinase-1 (tissue collagenase) production and collagenolytic activity in human vascular smooth muscle cells."Int J Mol Med. 8. 561-566 (2001)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Kato S, Ueda S, Tamaki K, Fujii M, Miyazono K, ten Dijke P, Morimatsu M, Okuda S.: "Ectopic expression of Smad7 inhibits transforming growth factor-b responses in vascular smooth muscle cells."Life Sci. 69. 2641-2652 (2001)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Okamato M, Kato S, Oizumi K, Kinoshita M, Inoue Y, Hoshino K, Akira S, Mckenzie ANJ, Young HA, Hoshino T.: "IL-18 in synergy with IL-2 induces lethal lung injury in mice : A potential role for cytokines, chemokines and NK cells in the pathologenesis of interstitial pneumonia."Blood. 99. 1289-1299 (2001)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Hiraoka K, Zenmyo M, Komiya S, Kawabata R, Yokouchi M, Suzuki R, Hamada T, Kato S, Nagata K.: "Relationship of p21 (waf1/cip1) and differentiation in chondrosarcoma cells."Virchowa Arch. 440. 285-290 (2002)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Aoki T, Kato S, Fox FC, Okamoto K, Sakata K, Morimatsu M, Shigemori M.: "Inhibition of autocrine fibroblast growth factors signaling by the adenovirus-mediated expression of an antisense trangene or a dominant negative receptor in human glioma cells in vitro."Int J Oncol. 21. 629-636 (2002)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Sakata K, Kato S, Fox JC, Shigemori M, Morimatsu M.: "Autocrine singaling through Ras regulates cells survival activity in human glioma cells : Potential cross-talk between Ras and the phosphatidylinositol 3-kinase-Akt pathway."J Neuropath Exp Neurol. 61. 975-983 (2002)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Ueda S, Kato S, Matsuoka H, Kimoto M, Okuda S, Morimatsu M, Imaizumi T.: "Regulation of Cytokine-induced Nitric Oxide Synthesis by Asymmetric Dimethylarginine : Role of Dimethylarginine Dimethylaminohydrolase."Circ Res. 92. 226-233 (2003)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Ikedo H, Tamaki K, Ueda S, Kato S, Fujii M, ten Dijke P, Okuda S.: "Smad protein and TGF-β signaling in vascular smooth muscle cells."Int J Mol Med. 11. 645-650 (2003)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Shibata R, Kai H, Seki Y, Kato S, Wada Y, Hanakawa Y, Hasimoto K, Yoshimura A, Imaizumi T.: "Inhibition of STAT3 prevents neointima formation by inhibiting proliferation and promoting apoptosis of neointimal smooth muscle cells."Hum Gene Ther. 14. 601-610 (2003)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Kato S, Ueda S, Yamaguchi M, Miyamoto T, Fujii T, Izumaru S, Kume S, Toyozumi Y, Arima N, Morimatsu M.: "Overexpression of p21 Waf1 induces apoptosis in immortalized human vascular smooth muscle cells."J Atheroscler Thromb. 10. 239-245 (2003)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Kawase Y, Hoshino T, Yokota K, Kuzuhara A, Kiril Y, Nishiwaki E, Yu Maeda, Junji Takeda J, Okamoto M, Kato S, Imaizumi T, Aizawa H, Yoshino K.: "Exacerbated and Prolonged Allergic and Non-Allergic Inflammatory Cutaneous Reaction in Mice with Targeted IL-18 Expression in the Skin."J Invest Dermatol. 121. 502-509 (2003)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Koga A, Oka N, Kikuchi T, Miyazaki H, Kato S, Imaizumi T.: "Adenovirus-mediated overexpression of caveolin-3 inhibits rat cardiomyocyte hypertrophy."Hypertension. 42. 213-219 (2003)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Hoshino T, Nakamura H, Okamoto M, Kato S, Araya S, Nomiyama K, Oizumi K, Young HA. Aizawa H, Yodoi J.: "Redox-Active Protein Thioredoxin Prevents Proinflammatory Cytokin-or Bleomycin-Induced Lung Injury."Am J Resp Crit Care. 168. 1075-1083 (2003)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Hanada T, Yoshida H, Kato S, Tanaka K, Masutani K, Tsukada J, Nomura Y, Mimata H, Kubo M, Yoshimura A.: "Suppressor of cytokine signaling-1 (SOCS1) is essential for suppressing dendritic cell activation and systemic autoimmunity."Immunity. 19. 437-450 (2003)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Izumaru S, Arima N, Toyozumi Y, Kato S, Morimatsu M, Nakashima T.: "Down-regulation of p21 Waf-1 protein facilitates IR-and UV-induced apoptosis in human squamous carcinoma cells."Int J Oncol. 24. 1245-1255 (2004)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Okamoto K, Kato S, Arima N, Fuji T, Morimatsu M, Imaizumi T.: "Cyclin-dependent kinase inhibitor, p21 Waf1, regulates vascular smooth muscle cell hypertrophy."Hypertension Research. 27. 283-291 (2004)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Fujii T, Kato S, Yamana H, Tanaka Y, Fujita H, Shirouzu K, Morimatsu M.: "Expression of G1 cell cycle markers and the effect of adenovirusmediated overexpression of p2lWaf-1 in squamous cell carcinoma of the esophagus."Int J Oncol.. 18. 157-163 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Shibata R, Kai, H Seki Y, Kato S.Morimatsu M, Kaibuchi K, Imaizumi T.: "Role of Rho-associated protein kinase in neointima formation after vascular injury."Circulation. 103. 284-289 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Zemmyo N, Komiya S, Hamada T, Hiraoka K, Kato S, Fujii T, Yano H, Irie K, Nagata K.: "Transcriptional activation of p21 by vitamine D3 or vitamine K2 leads to differentiation of p53-deficient MG-63 osteosarcoma cells."Hum Pathol. 32. 410-416 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Hamada T, Yoshida T, Kinjo I, Minoguchi S, Yasukawa H, Kato S, Miinata H, Nomura Y, Seki Y, Kubo M, Yoshimura A.: "A mutant form of JAB/SOCS1 auguments the cytokine-induced JAK/STAT pathway by accelerating degradation of wild-type JAB/CIS family proteins through the SOCS-box."J Biol Chem. 276. 40746-40754 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Wada Y, Kato S.Okamoto K, Izumaru S.Aoyagi S, Morimatsu M.: "Diltiazem, a calcium antagonist, inhibits matrix metalloproteinase-1 (tissue collagenase) production and collagenolytic activity in human vascular smooth muscle cells."Int J Mol Med. 8. 561-566 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Kato S, Ueda S, Tamaki K, Fujii M, Miyazono K, ten Dijke P, Morimatsu M, Okuda S.: "Ectopic expression of Smad7 inhibits transforming growth factor-b responses in vascular smooth muscle cells."Life Sci. 69. 2641-2652 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Okamato M, Kato S, Oizumi K, Kinoshita M, Inoue Y, Hoshino K, Akira S, Mckenzie ANJ, Young HA, Hoshino T.: "IL-18 in synergy with IL-2 induces lethal lung injury in mice : A potential role for cytokines, chemokines and NK cells in the pathologenesis of interstitial pneumonia."Blood. 99. 1289-1298 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Hiraoka K, Zenmyo M, Komiya 5, Kawabata R, Yokouchi M, Suzuki R, Hamada T, Kato S, Nagata K.: "Relationship of p21(waf1/cip1) and differentiation in chondrosarcoma cells."Virchows Arch. 440. 285-290 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Aoki T, Kato S, Fox FC, Okamoto K, Sakata K, Morimatsu M, Shigemon M.: "Inhibition of autocrine fibroblast growth factor signaling by the adenovirus-mediated expression of an antisense trangene or a dominant negative receptor in human glioma cells in vitro."Int J Oncol. 21. 629-636 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Sakata K, Kato_S, Fox JC, Shigemori M, Morimatsu M.: "Autocrine signaling through Ras regulates cell survival activity in human glioma cells : Potential cross-talk between Ras and the phosphatidylinositol 3-kinase-Akt pathway."J Neuropath Exp Neurol. 61. 975-983 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Ueda 5, Kato S, Matsuoka H, Kimoto M, Okuda S, Morimatsu M, Imaizumi T.: "Regulation of Cytokine-induced Nitric Oxide Synthesis by Asymmetric Dimethylarginine : Role of Dimethylarginine Dimethylaminohydrolase."Circ Res. 92. 226-233 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Ikedo H, Tamaki K, Ueda S.Kato S, Fujii M, ten Dijke P, Okuda S.: "Smad protein and TOP-p signaling in vascular smooth muscle cells"Int J Mol Med. 11. 645-650 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Shibata R,, Kai H, Seki Y, Kato S, Wada Y, Hanakawa Y, Hashimoto K, Yoshimura A, Imaizumi T.: "Inhibition of STAT3 prevents neointima formation by inhibiting proliferation and promoting apoptosis of neointimal smooth muscle cells."Hum Gene Ther. 14. 601-610 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Kato S, Ueda S, Yamaguchi M, Miyamoto T, Fujii T, Izumaru S, Kume 5, Toyozumi Y, Anma N, Morimatsu M.: "Overexpression of p2lWaf1 induces apoptosis in immortalized human vascular smooth muscle cells."J Atheroscler Thromb. 10. 239-245 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Kawase Y, Hoshino T, Yokota K, Kuzuhara A, Kirii Y, Nishiwaki E, Yu Maeda, Junji Takeda J, Okamoto M, Kato S. Imaizumi T, Aizawa H, Yoshino K.: "Exacerbated and Prolonged Allergic and Non-Allergic Inflammatory Cutaneous Reaction in Mice with Targeted IL-18 Expression in the Skin."J Invest Dermatol. 121. 502-509 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Koga A, Oka N, Kikuchi T, Miyazaki H, Kato S, Imaizumi T.: "Adenovirus-mediated overexpression of caveolin-3 inhibits rat cardiomyocyte hypertrophy."Hypertension. 42. 213-219 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Hoshino T, Nakamura H, Okamoto M, Kato S.Araya S, Nomiyama K, Oizumi K, Young HA.Aizawa H, Yodoi J.: "Redox-Active Protein Thioredoxin Prevents Proinflammatory Cytokine-or Bleomycin-Induced Lung Injury."Am J Resp Crit Care. 168. 1075-1083 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Hanada T, Yoshida H, Kato S.Tanaka K, Masutani K, Tsukada J, Nomura Y, Mimata H, Kubo M, Yoshimura A.: "Suppressor of cytokine signaling-1 (SOCS1) is essential [or suppressing dendritic cell activation and systemic autoimmunity."Immunity. 19. 437-450 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Izumaru S, Arima N, Toyozumi Y, Kato S, Morimatsu M, Nakashima T.: "Down-regulation of p21Waf-1 protein facilitates IR-and UV-induced apoptosis in human squamous carcinoma cells."Int J Oncol. 24. 1245-1255 (2004)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Okamoto K, Kato S, Arima N, Fujii T, Morimatsu M, Imaizumi T.: "Cyclin-dependent kinase inhibitor, p21Waf1, regulates vascular smooth muscle cell hypertrophy."Hypertension Research. 27. 283-291 (2004)

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

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Published: 2005-04-19  

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