Research of sphingosine kinase modification in acute lung injury

鞘氨醇激酶修饰在急性肺损伤中的研究

基本信息

批准号：
18590848
负责人：
NISHIMURA Yoshihiro
金额：
$ 2.57万
依托单位：
Kobe University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2006
资助国家：
日本
起止时间：
2006 至 2007
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-18590848/
关键词：
sphingosine 1-phosphate sphingosine kinase lung fibroblast bronchial asthma

项目摘要

The metabolism of sphingosine kinase (SPHK)/sphingosine 1-phosphate (SIP) system in lung diseases has been reported recently. In this project, we focused on the role of SPHK in lung epithelial cells and fibroblasts in injured lungs.1. We investigated the mechanism of myofibroblast differentiation in lung fibroblasts of acute lung injury. Bleomycin treatment increased SPHK expression and fibrotic changes in injured lungs. Our study reported that TGF-beta treatment increased SPHK1 activation in lung fibroblasts. S1P produced by SPHK1 induced the transactivation of S1P receptors and recruitment of activated RhoA. This data was accepted in Am J Respir Cell Mol Biol in 2007.2. Using mouse asthmatic model, we examined whether the effect of SPHK inhibitors attenuates airway inflammation. The inhalation of SPHK inhibitors by nebulizing maneuver showed significant decrease of airway hyperresponsiveness and eosinophilic inflammation induced by ovalbumin treatment, whereas intravenous delivery showed limited effects. Our data indicated that intratracheal treatment of SPHK inhibitor may be one of therapeutic approach for lung inflammation. This data was accepted in Am J Physiol Lung Cell Mol Physiol in 2008.3. In this animal model, we found that SPHK activity was increased in bronchial epithelial areas in asthmatic lungs. Then we examined the function of SPHK in goblet cell formation around epithelial walls. In vitro studies using airway liquid interface demonstrated that SPHK was activated and played a pivotal role in cell changes by IL-13 treatment. This data will be exhibited in American Thoracic Society in 2008. Thus, our studies clarified that SPHK works for morphological cell changes in lung inflammation.

肺部疾病中，鞘氨醇激酶（SPHK）/1-磷酸盐（SIP）系统的代谢。在这个项目中，我们专注于SPHK在肺上皮细胞中的作用和受伤的肺中成纤维细胞的作用。1。我们研究了急性肺损伤肺成纤维细胞中肌纤维细胞分化的机制。博来霉素治疗增加了肺部受伤的SPHK表达和纤维化变化。我们的研究报告说，TGF-β治疗增加了肺成纤维细胞中的SPHK1激活。 SPHK1产生的S1P诱导了S1P受体的反式激活和激活的RhoA的募集。该数据在2007年在AM J呼吸器细胞Mol Biol中被接受。使用小鼠哮喘模型，我们检查了SPHK抑制剂的作用是否会减轻气道炎症。通过雾化动作对SPHK抑制剂吸入抑制剂显示出卵巢蛋白治疗引起的气道高反应性和嗜酸性炎症的显着降低，而静脉内递送的影响有限。我们的数据表明，气管内治疗SPHK抑制剂可能是肺部炎症的治疗方法之一。该数据在2008年在AM J Physiol肺细胞Mol Physiol中接受。在这种动物模型中，我们发现哮喘肺的支气管上皮区域中SPHK活性增加。然后，我们检查了SPHK在上皮壁周围的杯状细胞形成中的功能。使用气道液体界面的体外研究表明，通过IL-13处理，SPHK被激活并在细胞变化中起关键作用。该数据将于2008年在美国胸部学会中展出。因此，我们的研究澄清说，SPHK致力于肺部炎症的形态细胞变化。