Breakdown of Epithelial Barrier Integrity and Overdrive Activation of Alveolar Epithelial Cells in the Pathogenesis of Acute Respiratory Distress Syndrome and Lung Fibrosis

Figure 3

Schematic model of molecular mechanisms of deterioration of acute respiratory distress syndrome (ARDS) and lung fibrosis in epithelial cell-specific Pten-deficient lungs. The phosphorylation levels of Akt are elevated in the Pten-deficient alveolar epithelial cells (AECs) at baseline and after injury. After lung injury, epithelial cell-specific Pten-deficient lungs show increased expressions of pS6K, Snail, matrix metalloproteinase (MMP) 2, and membrane type 1-MMP (MT1-MMP) and decreased expressions of claudin-4, zonula occludens-1 (ZO-1), occludin, and laminin. These alterations of the expression levels of molecules in epithelial cell-specific Pten-deficient lungs result in intensified disruption of AEC integrity, failure of the normal reconstitution of AEC integrity, and a subsequent deterioration of ARDS and lung fibrosis. TGF-β1: transforming growth factor-beta 1.