A Role for Forkhead Box A1 in Acute Lung Injury

Forkhead box protein A1 (FoxA1) is an evolutionarily conserved winged helix transcription factor with diverse regulatory functions. However, little is known about the role of FoxA1 in acute lung injury (ALI) and pulmonary cell injury. In this study, an in vivo model was employed whereby rats were administered an intravenous injection of oleic acid (OA, 0.1 ml/kg), and alveolar type II epithelial cells (AT-2 cells) injury was induced by hydrogen peroxide (H2O2) in vitro. OA injection resulted in lung injury and AT-2 cells apoptosis in vivo. OA injection and H2O2 upregulated FoxA1 mRNA and protein in lung tissue of the in vivo ALI model and in H2O2 challenged AT-2 cells. Overexpression of FoxA1 promoted apoptosis, whereas FoxA1 deficiency, induced by antisense oligonucleotides, decreased AT-2 cells apoptosis induced by H2O2, as shown by flow cytometry. These results suggest that FoxA1 may play an important role in ALI by promoting apoptosis of pulmonary epithelial cells.