Hepatocyte growth factor protects small airway epithelial cells from apoptosis induced by tumor necrosis factor-α or oxidative stress
Hepatocyte growth factor protects small airway epithelial cells from apoptosis induced by tumor necrosis factor-α or oxidative stress
复制标题
DOI：
10.1203/01.pdr.0000134255.58638.59
复制
发表时间：
2004-09-01
影响因子：
3.6
通讯作者：
Nakazawa, S
中科院分区：
文献类型：
--
作者：
Okada, M;Sugita, K;Nakazawa, S
肝细胞生长因子（HGF）参与肺的形态发生和再生已被建立在体外和动物体内实验。在本研究中，使用人小气道上皮细胞系（SAEC）检测HGF对肿瘤坏死因子（TNF）-α或过氧化氢（H2 O2）诱导的肺上皮细胞损伤的保护活性。Western blot分析显示，SAEC表面高表达HGF受体（c-Met），其下游信号转导通路功能正常。SAEC被TNF-α或H2 O2以剂量依赖性方式诱导凋亡，但在HGF存在下被显著地从凋亡中拯救。HGF的效果是明显的，不仅在同一时间，而且在治疗后几个小时内加入。HGF对TNF-α或H2 O2诱导的细胞凋亡的这种保护活性至少部分是通过上调核因子κ B活性和增加细胞凋亡抑制蛋白与细胞凋亡诱导蛋白的比例来介导的。这些结果表明，给予HGF可能在体内表现出有效的功能，用于保护和改善由炎症和/或氧化应激诱导的急性和慢性肺损伤。
Involvement of hepatocyte growth factor (HGF) in lung morphogenesis and regeneration has been established by in vitro and in vivo experiments in animals. In the present study, the protective activity of HGF against tumor necrosis factor (TNF)-alpha or hydrogen peroxide (H2O2)-induced damage of pulmonary epithelial cells was examined using the human small airway epithelial cell line (SAEC). Western blot analysis revealed that the receptor for HGF (c-Met) was highly expressed on the surface of SAEC and its downstream signal transduction pathway was functional. The SAEC was induced into apoptosis by the treatment with TNF-alpha or H2O2 in a dose-dependant manner, but was significantly rescued from apoptosis in the presence of HGF. The HGF effect was evident when added not only at the same time but also within several hours after treatment. This protective activity of HGF against the TNF-alpha- or H2O2-induced apoptosis was mediated, at least in part, by up-regulating the nuclear factor kappaB activity and an increase in the ratio of apoptosis-suppressing to apoptosis-inducing proteins. These results suggest that administration of HGF might exhibit a potent function in vivo for protection and improvement of acute and chronic lung injuries induced by inflammation and/or oxidative stress.