Urokinase induces its own expression in Beas2B lung epithelial cells.
Urokinase induces its own expression in Beas2B lung epithelial cells.
复制标题
DOI：
10.1152/ajplung.00395.2001
复制
发表时间：
2002-08
期刊：
影响因子：
--
通讯作者：
S. Shetty;U. Pendurthi;P. S. Halady;A. Azghani;S. Idell
中科院分区：
文献类型：
--
作者：
S. Shetty;U. Pendurthi;P. S. Halady;A. Azghani;S. Idell
尿激酶型纤溶酶原激活剂（uPA）与其受体（uPAR）相互作用，促进局部蛋白水解以及细胞增殖和迁移。这些功能有助于肺部炎症和重塑的发病机制以及肺肿瘤的生长和侵袭。在这项研究中，我们试图确定uPA是否改变其自身在肺上皮细胞中的表达。使用免疫沉淀和Western和北方印迹技术，我们发现，uPA处理增强uPA在Beas 2B肺上皮细胞中的表达在时间和浓度依赖性的方式。uPA表达的诱导通过其细胞表面受体uPAR介导，并且不需要uPA酶活性。uPA的氨基末端片段缺乏催化结构域，足以诱导uPA表达。丝氨酸蛋白酶纤溶酶和蛋白酶抑制剂抑肽酶未能改变uPA介导的uPA表达，而α-凝血酶增强的反应。用酪氨酸激酶抑制剂除莠霉素预处理Beas 2B细胞，表明酪氨酸激酶的激活参与uPA介导的uPA表达。肺源性上皮细胞暴露于uPA诱导uPA表达是一种新定义的途径，通过该途径，这种蛋白酶可以影响局部纤溶活性的表达和与肺部炎症或肿瘤密切相关的其他uPA依赖性细胞反应。
The urokinase-type plasminogen activator (uPA) interacts with its receptor (uPAR) to promote local proteolysis as well as cellular proliferation and migration. These functions contribute to the pathogenesis of lung inflammation and remodeling as well as the growth and invasiveness of lung neoplasms. In this study, we sought to determine if uPA alters its own expression in lung epithelial cells. Using immunoprecipitation and Western and Northern blotting techniques, we found that uPA treatment enhanced uPA expression in Beas2B lung epithelial cells in a time- and concentration-dependent manner. The induction of uPA expression is mediated through its cell surface receptor uPAR and does not require uPA enzymatic activity. The amino-terminal fragment of uPA, lacking the catalytic domain, is sufficient to induce uPA expression. The serine protease plasmin and the protease inhibitor aprotinin failed to alter uPA-mediated uPA expression, whereas alpha-thrombin potentiated the response. Pretreatment of Beas2B cells with a tyrosine kinase inhibitor, herbimycin, suggests that activation of tyrosine kinase(s) is involved in the uPA-mediated uPA expression. Induction of uPA expression by exposure of lung-derived epithelial cells to uPA is a newly defined pathway by which this protease could influence expression of local fibrinolytic activity and other uPA-dependent cellular responses germane to lung inflammation or neoplasia.