MODULATION OF OXIDANT INJURY BY FGF-10

FGF-10 对氧化损伤的调节

• 批准号: 6656822
• 负责人: DAYA UPADHYAY
• 金额: $ 5.44万
• 依托单位: STANFORD UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-09-30 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/6656822
• 关键词: DNA damage; apoptosis; fibroblast growth factor; hydrogen peroxide; laboratory rat; mitogen activated protein kinase; oxidative stress; postdoctoral investigator; respiratory epithelium; sodium potassium exchanging ATPase; tissue /cell culture

Alveolar epithelial cell (AEC) injury and repair are important in the pathogenesis of oxidant-induced lung damage. Recent investigations have demonstrated that growth factors have a critical role in preventing oxidant-induced lung injury. However the mechanisms involved are multiple and not well defined. Growth factors may decrease oxidant-- induced lung injury by preventing DNA damage (an early indicator of oxidant stress), apoptosis, and down regulation o Na, K-ATPase in AEC. Mitogen-activated protein kinase cascade is triggered by growth factors resulting in cell proliferation and differentiation. The recently described growth factor Fibroblast growth factor-10, is a potent mitogen for rat ATII cell (alveolar Type II cells). Fibroblast Growth Factor-10 (FGF-10) is predominantly expressed in the lung and is required for the lung development. The biological role of this novel FGF is yet to be elucidated. Our preliminary data show that FGF-10 attenuates H202- induced A549 cells DNA damage and cell death. The Specific aims of this proposal are 1) To determine whether FGF-10 prevents H202- induced ATII cells DNA damage and apoptosis. 2) To determine whether FGF-10 improves H202-induced Na,K-ATPase downregulation in AEC. 3) To determine whether FGF-10 attenuates H202-induced AEC DNA damage and Na,K-ATPase downregulation by activation of the MAPK signaling pathways. My proposed work will enable me to understand the molecular and biological basis of the pathophysiology of acute respiratory distress syndrome and pulmonary fibrosis.

肺泡上皮细胞（AEC）损伤和修复在氧化剂引起的肺损伤的发病机制中很重要。最近的研究表明，生长因子在预防氧化剂引起的肺损伤中发挥着关键作用。然而，所涉及的机制是多种多样的并且没有明确定义。生长因子可以通过防止 DNA 损伤（氧化应激的早期指标）、细胞凋亡和 AEC 中 Na、K-ATP 酶的下调来减少氧化诱导的肺损伤。丝裂原激活的蛋白激酶级联由生长因子触发，导致细胞增殖和分化。最近描述的生长因子成纤维细胞生长因子-10 是大鼠 ATII 细胞（肺泡 II 型细胞）的有效有丝分裂原。成纤维细胞生长因子-10 (FGF-10) 主要在肺部表达，是肺部发育所必需的。这种新型 FGF 的生物学作用尚未阐明。我们的初步数据表明，FGF-10 可减轻 H202 诱导的 A549 细胞 DNA 损伤和细胞死亡。该提案的具体目的是 1) 确定 FGF-10 是否可以防止 H202 诱导的 ATII 细胞 DNA 损伤和凋亡。 2)确定FGF-10是否改善AEC中H2O2诱导的Na,K-ATP酶下调。 3)确定FGF-10是否通过激活MAPK信号通路来减轻H2O2诱导的AEC DNA损伤和Na,K-ATP酶下调。我提出的工作将使我能够了解急性呼吸窘迫综合征和肺纤维化病理生理学的分子和生物学基础。