| Project/Area Number |
15590236
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
General pharmacology
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| Research Institution | Hoshi University |
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Principal Investigator |
MISAWA Miwa Hoshi University, Department of Pharmacology, School of Pharmacy, 薬理学教室, 教授 (20061294)
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| Co-Investigator(Kenkyū-buntansha) |
CHIBA Yoshihiko Hoshi University, Department of Pharmacology, School of Pharmacy, 薬理学教室, 講師 (00287848)
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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 |
¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2005: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 2004: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 2003: ¥2,200,000 (Direct Cost: ¥2,200,000)
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| Keywords | bronchial asthma / airway hyperresponsiveness / Ca^<2+> sensitization / RhoA / CPI-17 / rhoA mRNA / cpi-17 mRNA / membrane tranlocation / 膜translacetion / endothelin / TNFα / 転写因子 |
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| Research Abstract |
(1)The authors have found for the first time that expression of rhoA mRNA and upregulation of RhoA protein in bronchial smooth muscle of airway hyperresponsive (AHR) rats which received repeated antigen-challenge. We propose that enhanced Ca^<2+> sensitization induced by such RhoA protein activation may evoke the AHR. (2)Transcriptional factors involved in RhoA protein expression were investigated by protein/DNA array. Stat5,CDP,HSE,SBE,SIE and CBF were observed to be activated at AHR state. (3)TNF-a detected in broncho-alveolar fluid of asthmatics enhanced the bronchosonstriction by ACh, which accompanied with increases in rhoA mRNA and protein. (4)Translocation of RhoA protein from cytosol to plasma membrane was observed after ACh stimulation of bronchial cells, suggesting an activation of RhoA by ACh. (5)Another protein CPI-17 involved in Ca^<2+> sensitization as well as RhoA was also increased in the AHR bronchial smooth muscle. Therefore, RhoA/Rho-kinase/CPI-17 cross-pathway might work at Ca^<2+> sensitization of bronchial smooth muscle of AHR rats.
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