Phosphatase and tensin homolog deleted on chromosome 10 (PTEN) reduces vascular endothelial growth factor expression in allergen-induced airway inflammation
Phosphatase and tensin homolog deleted on chromosome 10 (PTEN) reduces vascular endothelial growth factor expression in allergen-induced airway inflammation
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DOI：
10.1124/mol.106.022228
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发表时间：
2006-06-01
影响因子：
3.6
通讯作者：
Lee, Yong Chul
中科院分区：
文献类型：
--
作者：
Lee, Kyung Sun;Kim, So Ri;Lee, Yong Chul
血管内皮生长因子（VEGF）在支气管哮喘的发病机制中起关键作用。10号染色体上缺失的磷酸酶和张力蛋白同源物（PTEN）已经涉及通过磷酸肌醇3-激酶（PI 3 K）/Akt途径调节细胞存活信号传导。PI 3 K在VEGF介导的信号转导中的关键作用得以确立。然而，在哮喘中PTEN对VEGF介导的信号传导的影响尚不清楚.本研究旨在确定PI 3 K抑制剂和PTEN对过敏原诱导的气道炎症中VEGF表达的影响。我们使用雌性C57 BL/6小鼠哮喘模型来确定PTEN在过敏原诱导的气道炎症中的作用，特别是在VEGF的表达中。过敏原诱导的气道炎症导致肺组织中PI 3 K活性增加。这些小鼠在肺中发展出以下典型的哮喘病理生理学特征：气道炎性细胞数量增加;气道高反应性;白细胞介素（IL）-4、IL-5、IL-13、细胞间粘附分子1、血管细胞粘附分子1、活化正常T细胞表达和分泌的调节因子（RANTES）和嗜酸性粒细胞趋化因子的表达增加;血管通透性增加;以及VEGF水平升高。给予PI 3 K抑制剂或携带PTEN cDNA的腺病毒可减轻哮喘症状，并降低过敏原诱导的哮喘肺中血浆外渗和VEGF水平的升高。这些结果表明，在过敏原诱导的气道炎症中，PTEN减少VEGF表达。
Vascular endothelial growth factor (VEGF) plays a pivotal role in the pathogenesis of bronchial asthma. Phosphatase and tensin homolog deleted on chromosome 10 (PTEN) has been implicated in regulating cell survival signaling through the phosphoinositide 3-kinase (PI3K)/Akt pathway. The key role of PI3K in VEGF-mediated signal transduction is established. However, the effects of PTEN on VEGF- mediated signaling in asthma are unknown. This study aimed to determine the effect of PI3K inhibitors and PTEN on VEGF expression in allergen-induced airway inflammation. We have used a female C57BL/6 mouse model for asthma to determine the role of PTEN in allergen-induced airway inflammation, specifically in the expression of VEGF. Allergen-induced airway inflammation leads to increased activity of PI3K in lung tissue. These mice develop the following typical pathophysiological features of asthma in the lungs: increased numbers of inflammatory cells of the airways; airway hyper-responsiveness; increased expression of interleukin (IL)-4, IL-5, IL-13, intercellular adhesion molecule 1, vascular cell adhesion molecule 1, regulated on activation normal T cell expressed and secreted (RANTES), and eotaxin; increased vascular permeability; and increased levels of VEGF. Administration of PI3K inhibitors or adenoviruses carrying PTEN cDNA reduced the symptoms of asthma and decreased the increased levels of plasma extravasation and VEGF in allergen-induced asthmatic lungs. These results indicate that PTEN reduces VEGF expression in allergen-induced airway inflammation.