2007 Fiscal Year Final Research Report Summary
Development of in vivo biosensors using genetic engineering
| Project/Area Number |
16390243
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Kidney internal medicine
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| Research Institution | University of Yamanashi |
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Principal Investigator |
KITAMURA Masanori University of Yamanashi, Interdisciplinary Gmduaie School of Medicine and Engineering, Professor (90333062)
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| 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)
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| Project Period (FY) |
2004 – 2007
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| Keywords | biosensor / inflammation / endonlasmic reticulum stres / secreted alkaline nhosohatase / transeenic mouse / heavy metal toxicity / endotoxemia / signal transduction |
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| 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
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Research Products
(24 results)
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[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
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Journal Title
J Biol Chem 283
Pages: 4252-4260
Description
「研究成果報告書概要(欧文)」より
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[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
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Journal Title
FEBS Lett 581
Pages: 2055-2059
Description
「研究成果報告書概要(欧文)」より
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[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
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Journal Title
Cell Death Differ 14
Pages: 1467-1474
Description
「研究成果報告書概要(欧文)」より
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[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
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Journal Title
J Immunol 176
Pages: 2529-2537
Description
「研究成果報告書概要(欧文)」より
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[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
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Journal Title
Nucleic Acids Res 34
Pages: e93
Description
「研究成果報告書概要(欧文)」より
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[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
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Journal Title
Anal Biochem 339
Pages: 249-256
Description
「研究成果報告書概要(欧文)」より
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[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
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Journal Title
Kidney Int 68
Pages: 886-893
Description
「研究成果報告書概要(欧文)」より
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[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
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Journal Title
Lab Invest 85
Pages: 1429-1439
Description
「研究成果報告書概要(欧文)」より
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[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
Year and Date
20071211-15
Description
「研究成果報告書概要(欧文)」より
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[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
Year and Date
20061114-19
Description
「研究成果報告書概要(欧文)」より
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[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
Year and Date
20061114-19
Description
「研究成果報告書概要(欧文)」より
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