| Project/Area Number |
15390030
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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 |
Biological pharmacy
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| Research Institution | Kumamoto University |
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Principal Investigator |
MIYATA Takeshi Kumamoto University, Graduate School of Pharmaceutical Sciences, Department of Chemico-Pharmacological Sciences, Professor, 大学院・医学薬学研究部, 教授 (90040310)
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| Co-Investigator(Kenkyū-buntansha) |
TAKAHAMA Kazuo Kumamoto University, Graduate School of Pharmaceutical Sciences, Department of Environmental and Molecular Health Sciences, Professor, 大学院・医学薬学研究部, 教授 (80150548)
KAI Hirofumi Kumamoto University, Graduate School of Pharmaceutical Sciences, Department of Molecular Medicine, Professor, 大学院・医学薬学研究部, 教授 (30194658)
ISOHAMA Yoichiro Kumamoto University, Graduate School of Pharmaceutical Sciences, Department of Chemico-Pharmacological Sciences, Associate Professor, 大学院・医学薬学研究部, 助教授 (10240920)
TOKUTOMI Naofumi Sojo University, Faculty of pharmaceutical Sciences, Laboratory of Pharmacology, Professor, 薬学部, 教授 (30227582)
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| Project Period (FY) |
2003 – 2005
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| Project Status |
Completed (Fiscal Year 2005)
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| Budget Amount *help |
¥15,000,000 (Direct Cost: ¥15,000,000)
Fiscal Year 2005: ¥4,300,000 (Direct Cost: ¥4,300,000)
Fiscal Year 2004: ¥4,500,000 (Direct Cost: ¥4,500,000)
Fiscal Year 2003: ¥6,200,000 (Direct Cost: ¥6,200,000)
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| Keywords | COPD / Neutrophil elastase / Airway Inflammation / Glucocorticoid / Tanscription factor / COPD / グリチルリチン / 気道粘液 / Sp1転写因子 / レチノイン酸 / 杯細胞 / 肺胞上皮細胞 / Sp3転写因子 / aquaporin-5 / MUC1ムチン / 慢性閉塞性呼吸器疾患 / 肺上皮細胞 / 粘液遺伝子 / ETS転写因子 / GM-CSF |
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| Research Abstract |
To develop a new therapeutic way in chronic obstructive pulmonary disease, we have studied the regulatory mechanisms of various functions in lung epithelial cells. The findings in this study were summarized below.
1)Sp1, Sp3 and ETS transcription factors regulate transdifferentiation from alveolar type II to type I epithelial cells. Sp1 increased type I cell-specific gene expression, and Sp3 competitively inhibited the effect of Sp1. In addition, the activity of ETS transcription factor, MEF, was controlled by protein kinase C.
2)Lipopolysaccaride changed subcellualr sidtribution of aquaporin-5, a water channel protein in alveolar type I cells, from intracellular vesicle compartment to plasma membrane, which is mediated by p38 MAP kinase.
3)Glucocorticoid is the most effective to treat the lung inflammation, but severe adverse effects of glucocorticoid restricts its chronic use. We found that glycyrrhizin (GL) has glucocorticoid-like transcriptional regulatory effect the without activating glucocorticoid receptor, using in vitro reporter gene assay. The glucocorticoid-like effect of GL was confirmed in several in vivo studies, GL strongly inhibited lung inflammation as well as glucocorticoid, but did not decrease body weight and thymus volume.
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