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.
