• Search Research Projects
  • Search Researchers
  • How to Use
  1. Back to previous page

Development of in vivo biosensors using genetic engineering

Research Project

Project/Area Number 16390243
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Kidney internal medicine
Research InstitutionUniversity of Yamanashi

Principal Investigator

KITAMURA Masanori  University of Yamanashi, Interdisciplinary Gmduaie School of Medicine and Engineering, Professor (90333062)

Co-Investigator(Kenkyū-buntansha) YAO Jian  University of Fukui, Interdisciplinary Graduate School of Medicine and Engineering, Associate Professor (50303128)
TAKEDA Masayuki  University of Fukui, Interdisciplinary Gradne School of Medicine and Engineering, Professor (80197318)
Project Period (FY) 2004 – 2007
Project Status Completed (Fiscal Year 2007)
Budget Amount *help
¥14,950,000 (Direct Cost: ¥14,200,000、Indirect Cost: ¥750,000)
Fiscal Year 2007: ¥3,250,000 (Direct Cost: ¥2,500,000、Indirect Cost: ¥750,000)
Fiscal Year 2006: ¥2,500,000 (Direct Cost: ¥2,500,000)
Fiscal Year 2005: ¥2,500,000 (Direct Cost: ¥2,500,000)
Fiscal Year 2004: ¥6,700,000 (Direct Cost: ¥6,700,000)
Keywordsbiosensor / inflammation / endonlasmic reticulum stres / secreted alkaline nhosohatase / transeenic mouse / heavy metal toxicity / endotoxemia / signal transduction / 急性腎不全 / 重金属 / シゲナル伝達 / 病理 / 遺伝子導入 / 遺伝子治療 / NF-kB / 糸球体腎炎 / 分泌型アルカリフォスファター / 細胞移植 / NF-κB / メサンギウム細胞 / 分泌方アルカリフォスファターゼ
Research Abstract

1. Monitoring of inflammation Using an inflammation-responsive regulatory element as a molecular sensor, we established a cell-based biosensor for continuous, non-invasive monitoring of local microscopic inflammation in vivo. Glomerulonephritis was used as a model of local inflammation. Mesangial cells were stably transfected with a marker gene encoding secreted alkaline phosphatase (SEAP) under the control of the KB enhancer elements. The established sensor cells were transferred selectively into rat glomeruli via the renal circulation. After induction of acute glomerulonephritis (anti-Thy 1.1 nephritis), the serum level of SEAP was increased transiently in cell-transferred nephritic rats. The kinetics of serum SEAP was closely correlated with the natural course of the inflammation. These results suggested that, without invasive procedures like tissue biopsies, continuous, real-time monitoring of microscopic inflammation is feasible in vivo via locally created, cell-based biosensors.
2 … More . Monitoring of endoplasmic reticulum (ER) stress We found that activity of ER stress-responsive alkaline phosphatase (ES-TRAP) produced by transfected cells is rapidly downregulated by ER stress independent of transcriptional regulation. This phenomenon was observed in a wide range of cell types triggered by various ER stress inducers, and the magnitude of the decrease in ES-TRAP was proportional to the extent of ER stress. In transgenic mice constitutively producing ES-TRAP, systemic induction of ER stress by thapsigargin led to reduction in serum ES-TRAP activity. In these mice, administration with lipopolysaccharide and cadmium also caused rapid, transient decrease in serum ES-TRAP activity, and it was correlated with up-regulation of endogenous ER stress markers in several organs. These results elucidated for the first time a possible involvement of ER stress in endotoxemia and toxicity of heavy metal and provided evidence for usefulness of ES-TRAP for continuous, real-time monitoring of ER stress in vivo. Less

Report

(5 results)
  • 2007 Annual Research Report   Final Research Report Summary
  • 2006 Annual Research Report
  • 2005 Annual Research Report
  • 2004 Annual Research Report
  • Research Products

    (42 results)

All 2008 2007 2006 2005 2004 Other

All Journal Article (32 results) (of which Peer Reviewed: 11 results) Presentation (7 results) Remarks (2 results) Patent(Industrial Property Rights) (1 results) (of which Overseas: 1 results)

  • [Journal Article] Involvement of selective reactive oxygen species upstream of proapoptotic branches of unfolded protein response.2008

    • Author(s)
      Yokouchi M, et. al.
    • Journal Title

      J Biol Chem 283

      Pages: 4252-4260

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] Involvement of selective reactive oxygen species upstream of proapoptotic branches of unfolded protein response2008

    • Author(s)
      Yokouchi, M., Hiramatsu, N., Hayakawa, K., Okamura, M., Du, S., Kasai, A., Takano, Y., Shitamura, A., Shimada, T., Yao, J., Kitamura, M
    • Journal Title

      J Biol Chem 283

      Pages: 4252-4260

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Involvement of selective reactive oxygen species upstream of proapoptotic branches of unfolded protein response.2008

    • Author(s)
      Yokouchi M, Hiramatsu N, Hayakawa K, Okamura M, Du S, Kasai A, Takano Y, Shitamura A, Shimada T, Yao J, Kitamura M
    • Journal Title

      J Biol Chem 283

      Pages: 4252-4260

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Rapid, transient induction of ER stress in the liver and kidney after acute exposure to heavy metal: Evidence from transgenic sensor mice.2007

    • Author(s)
      Hiramatsu N, et. al.
    • Journal Title

      FEBS Lett 581

      Pages: 2055-2059

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] Atypical, bidirectional regulation of cadmium-induced apoptosis via distinct signaling of unfolded protein response.2007

    • Author(s)
      Yokouchi M, et. al.
    • Journal Title

      Cell Death Differ 14

      Pages: 1467-1474

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] Rapid, transient induction of ER stress in the liver and kidney after acute exposure to heavy metal : Evidence from transgenic sensor mice2007

    • Author(s)
      Hiramatsu, N., Kasai, A., Du, S., Takeda, M., Hayakawa, K., Okamura, M., Yao, J., Kitamura, M
    • Journal Title

      FEBS Lett 581

      Pages: 2055-2059

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Atypical, bidirectional regulation of cadmium-induced apoptosis via distinct signaling of unfolded protein response2007

    • Author(s)
      Yokouchi, M., Hiramatsu, N., Hayakawa, K., Kasai, A., Takano, Y., Yao, J., Kitamura, M
    • Journal Title

      Cell Death Differ 14

      Pages: 1467-1474

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Rapid, transient induction of ER stress in the liver and kidney after acute exposure to heavy metal: Evidence from transgenic sensor mice.2007

    • Author(s)
      Hiramatsu N, Kasai A, Du S, Takeda M, Hayakawa K, Okamura M, Yao J, Kitamura M
    • Journal Title

      FEBS Lett 581

      Pages: 2055-2059

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Atypical,bidirectional regulation of cadmium-induced apoptosis via distinct signaling of unfolded protein response.2007

    • Author(s)
      Yokouchi M, Hiramatsu N, Hayakawa K, Kasai A, Takano Y, Yao J, Kitamura M
    • Journal Title

      Cell Death Differ 14

      Pages: 1467-1474

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Priming of glomerular mesangial cells by activated macrophages causes blunted responses to proinflammatory stimuli.2006

    • Author(s)
      Hayakawa K, et. al.
    • Journal Title

      J Immunol 176

      Pages: 2529-2537

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] Real-time detection and continuous monitoring of ER stress in vitro and in vivo by ES-TRAP: Evidence for systemic, transient ER stress during endotoxemia.2006

    • Author(s)
      Hiramatsu N, et. al.
    • Journal Title

      Nucleic Acids Res 34

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] Priming of glomerular mesangial cells by activated macrophages causes blunted responses to proinflammatory stimuli2006

    • Author(s)
      Hayakawa, K., Meng, Y., Hiramatsu, N., Kasai, A., Yamauchi, K., Yao, J., Kitamura, M
    • Journal Title

      J Immunol 176

      Pages: 2529-2537

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Real-time detection and continuous monitoring of ER stress in vitro and in vivo by ES-TRAP : Evidence for systemic, transient ER stress during endotoxemia2006

    • Author(s)
      Hiramatsu, N., Kasai, A., Hayakawa, K., Yao, J., Kitamura, M
    • Journal Title

      Nucleic Acids Res 34

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Priming of glomerular mesangial cells by activated macrophages causes blunted responses to proinflammatory stumuli.2006

    • Author(s)
      Hayakawa K et al.
    • Journal Title

      J Immunol 176

      Pages: 2529-2537

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Screening and identification of substances that regulate nephrin gene expression using engineered reporter podocytes.2006

    • Author(s)
      Yamauch K et al.
    • Journal Title

      Kidney Int 70

      Pages: 892-900

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Spontaneous activation of the NF-kB signaling pathway in isolated normal glomeruli.2006

    • Author(s)
      Hayakawa K et al.
    • Journal Title

      Am J Physiol - Renal 291

    • Related Report
      2006 Annual Research Report
  • [Journal Article] High levels of dioxin-like potential in cigarette smoke evidenced by in vitro and in vivo biosensing2006

    • Author(s)
      Kasai A et al.
    • Journal Title

      Cancer Res 66

      Pages: 7143-7150

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Real-time detection and continuous monitoring of ER stress in vitro and in vivo by ES-TRAP : Evidence for systemic, transient ER stress during endotoxemia.2006

    • Author(s)
      Hiramatsu N et al.
    • Journal Title

      Nucleic Acids Res 34

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Secreted protein-based reporter systems for monitoring inflammatory events : Critical interference by endoplasmic reticulum stress.2006

    • Author(s)
      Hiramatsu N et al.
    • Journal Title

      J Immunol Methods 315

      Pages: 202-207

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Priming of glomerular mesangial cells by activated macrophages causes blunted responses to proinflammatory stimuli.2006

    • Author(s)
      Hayakawa K et al.
    • Journal Title

      J Immunol In press

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Alkaline phosphatase vs. luciferase as secreted reporter molecules in vivo.2005

    • Author(s)
      Hiramatsu N, et. al.
    • Journal Title

      Anal Biochem 339

      Pages: 249-256

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] Real-time monitoring of mesangial cell-macrophage cross-talk using SEAP in vitro and ex vivo.2005

    • Author(s)
      Meng Y, et. al.
    • Journal Title

      Kidney Int 68

      Pages: 886-893

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] Continuous, non-invasive monitoring of local microscopic inflanmation using genetically engineered cell-based biosensor.2005

    • Author(s)
      Meng Y, et. al.
    • Journal Title

      Lab Invest 85

      Pages: 1492-1439

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] Alkaline phosphatase vs. luciferase as secreted reporter molecules in vivo2005

    • Author(s)
      Hiramatsu, N., Kasai, A., Meng, Y., Hayakawa, K., Yao, J., Kitamura, M
    • Journal Title

      Anal Biochem 339

      Pages: 249-256

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Real-time monitoring of mesangial cell - macrophage cross-talk using SEAP in vitro and ex vivo2005

    • Author(s)
      Meng, Y., Kasai, A., Hiramatsu, N., Hayakawa, K., Takeda, M., Shimizu, F., Kawachi, H., Yao, J., Kitamura, M
    • Journal Title

      Kidney Int 68

      Pages: 886-893

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Continuous, non-invasive monitoring of local microscopic inflanmation using genetically engineered cell-based biosensor2005

    • Author(s)
      Meng, Y., Kasai, A., Hiramatsu, N., Hayakawa, K., Yamauchi, K., Takeda, M., Kawachi, H., Shimizu, F., Yao, J., Kitamura, M
    • Journal Title

      Lab Invest 85

      Pages: 1429-1439

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Alkaline phosphatase vs.luciferase as secreted reporter molecules in vivo.2005

    • Author(s)
      Hiramatsu N et al.
    • Journal Title

      Anal Biochem 339

      Pages: 249-256

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Real-time monitoring of mesangial cell-macrophage cross-talk using SEAP in vitro and ex vivo.2005

    • Author(s)
      Meng Y et al.
    • Journal Title

      Kidney Int 68

      Pages: 886-893

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Enhancement of NF-κB activity by resveratrol in cytokine-exposed mesangial cells.2005

    • Author(s)
      Uchida Y et al.
    • Journal Title

      Clin Exp Immunol 142

      Pages: 76-83

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Continuous, noninvasive monitoring of local microscopic inflammation using a genetically engineered cell-based biosensor.2005

    • Author(s)
      Meng Y et al.
    • Journal Title

      Lab Invest 85

      Pages: 1429-1439

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Alkaline phosphatase vs. luciferase as secreted reporter molecules in vivo2005

    • Author(s)
      Nobuhiko Hiramatsu
    • Journal Title

      Analytical Biochemistry In press

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Genetic biosensors : Application for medicine, ecomanagement, and in vivo bioimaging2004

    • Author(s)
      Masanori Kitamura
    • Journal Title

      Recent Res.Devel.Biophys.Biochem. 4

      Pages: 1-13

    • Related Report
      2004 Annual Research Report
  • [Presentation] Rapid, transient induction of ER stress in the liver and kidney after acute exposure to heavy metal: Evidence from transgenic sensor mice.2007

    • Author(s)
      Kasai A, et. al.
    • Organizer
      BMB2007
    • Place of Presentation
      横浜
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] Rapid, transient induction of ER stress in the liver and kidney after acute exposure to heavy metal : Evidence from transgenic sensor mice2007

    • Author(s)
      Kasai, A., Hiramatsu, N., Du, S., Takeda, M., Hayakawa, K., Okamura, M., Yao, J., Kitamura, M
    • Organizer
      BMB 2007
    • Place of Presentation
      Yokohama, Japan
    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] Rapid,transient induction of ER stress in the liver and kidney after acute exposure to heavy metal: Evidence from transgenic sensor mice.2007

    • Author(s)
      Kasai A, Hiramatsu N, Du S, Takeda M, Hayakawa K, Okamura M, Yao J, Kitamura M
    • Organizer
      BMB2007
    • Place of Presentation
      横浜
    • Related Report
      2007 Annual Research Report
  • [Presentation] Real-time detection and continuous monitoring of ER stress in vitro and in vivo by ES-TRAP: Evidence for systemic, transient ER stress during endotoxemia.2006

    • Author(s)
      Hiramatsu N, et. al.
    • Organizer
      39th Annual Meeting of Am Soc Nephrol
    • Place of Presentation
      San Diego
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] Cadmium-induced apoptosis of renal tubular cells via endoplasmic reticulum stress: Involvement of selective unfolded protein responses.2006

    • Author(s)
      Yokouchi M, et. al.
    • Organizer
      39th Annual Meeting of Am Soc Nephrol
    • Place of Presentation
      San Diego
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] Real-time detection and continuous monitoring of ER stress in vitro and in vivo by ES-TRAP : Evidence for systemic, transient ER stress during endotoxemia2006

    • Author(s)
      Hiramatsu, N., Kasai, A., Hayakawa, K., Yao, J., Kitamura, M
    • Organizer
      39th Annual Meeting of Am Soc Nephrol
    • Place of Presentation
      San Diego
    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] Cadmium-induced apoptosis of renal tubular cells via endoplasmic reticulum stress : Involvement of selective unfolded protein responses2006

    • Author(s)
      Yokouchi, M., Hiramatsu, N., Hayakawa, K., Kasai, A., Takano, Y., Yao, J., Kitamura, M
    • Organizer
      39th Annual Meeting of Am Soc Nephrol
    • Place of Presentation
      San Diego
    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Remarks] 「研究成果報告書概要(和文)」より

    • URL

      http://www.med.yamanashi.ac.jp/clinical/molecular/

    • Related Report
      2007 Final Research Report Summary
  • [Remarks]

    • URL

      http://www.med.yamanashi.ac.jp/clinical/molecular/

    • Related Report
      2007 Annual Research Report
  • [Patent(Industrial Property Rights)] 特許権2006

    • Inventor(s)
      北村正敬
    • Industrial Property Rights Holder
      山梨大学
    • Filing Date
      2006-05-19
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Overseas

URL: 

Published: 2004-04-01   Modified: 2016-04-21  

Information User Guide FAQ News Terms of Use Attribution of KAKENHI

Powered by NII kakenhi