Studies on change in airway hyperresponsiveness at bronchial asthma using the technique of RhoA gene manipulation

RhoA基因操作技术研究支气管哮喘气道高反应性变化

• 批准号: 15590236
• 负责人: MISAWA Miwa
• 金额: $ 2.3万
• 依托单位: Hoshi University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2003
• 资助国家: 日本
• 起止时间: 2003 至 2005
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-15590236/
• 关键词: 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

(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.

(1)首次发现反复抗原攻击后的高反应性(AHR)大鼠支气管平滑肌RhoA基因表达和RhoA蛋白表达上调。我们认为这种RhoA蛋白的激活可能通过增强Ca~(2+)和Gt~(2+)的敏感性而引起AHR。(2)用蛋白质/DNA芯片研究RhoA蛋白表达的转录因子。在AHR状态下，STAT5、CDP、HSE、SBE、SIE和CBF被激活。(3)哮喘患者肺泡灌洗液中检测到的肿瘤坏死因子-α增强了ACh对支气管的收缩作用，并伴有RhoA基因和蛋白的表达增加。(4)ACh刺激后，RhoA蛋白从胞浆移位至质膜，提示ACh对RhoA有激活作用。(5)参与钙敏化和RhoA反应的另一种蛋白CPI-17在AHR的支气管平滑肌中也有增加。因此，RhoA/Rho-Kinase/CPI-17交叉通路可能参与AHR大鼠支气管平滑肌的钙增敏作用。

项目成果

Acetylcholine-induced phosphorylation and membrane translocation of CPI-17 in bronchial smooth muscle of rats

乙酰胆碱诱导大鼠支气管平滑肌CPI-17磷酸化和膜易位

• 发表时间: 2005
• 期刊: Am.J.Physiol.Lung Cell.Mol.Physiol. 289
• 作者: Sakai;H.;Hirano;T.;Chiba;Y.;Misawa;M.
• 通讯作者: M.

The role of RhoA-mediated Ca2+ sensitization of bronchial smooth muscle contraction in airway hyperresponsiveness

• DOI: 10.1540/jsmr.40.155
• 发表时间: 2004-10-01
• 期刊: Journal of Smooth Muscle Research
• 作者: Chiba, Yoshihiko;Misawa, Miwa
• 通讯作者: Misawa, Miwa

Abe, K., Misawa, M.: "The extracellular signal-regulated kinase cascade suppresses amyloid β protein-induced promotion of glutamate clearance"Brain Res. 979. 179-187 (2003)

Abe, K., Misawa, M.：“细胞外信号调节激酶级联抑制淀粉样蛋白 β 蛋白诱导的谷氨酸清除促进”Brain Res。 979. 179-187 (2003)

The role of RhoA-mediate Ca^<2+> sensitization of bronchial smooth muscle contraction in airway hyperresponsiveness

RhoA介导的Ca^<2>致敏支气管平滑肌收缩在气道高反应性中的作用

• 发表时间: 2004
• 期刊: J.Smooth Muscle Res. 40
• 作者: Chiba;Y.;Misawa;M.
• 通讯作者: M.

TNF-α augment the expression of RhoA in rat bronchus

TNF-α 增强大鼠支气管中 RhoA 的表达

• 发表时间: 2004
• 期刊: J.Smooth Muscle Res. 40
• 作者: Sakai;H.;Otogoto;S.;Chiba;Y.;Abe;K.;Misawa;M.
• 通讯作者: M.