| First Author | Kalinichenko VV | Year | 2002 |
| Journal | Am J Physiol Lung Cell Mol Physiol | Volume | 282 |
| Issue | 6 | Pages | L1253-65 |
| PubMed ID | 12003781 | Mgi Jnum | J:77019 |
| Mgi Id | MGI:2180909 | Doi | 10.1152/ajplung.00463.2001 |
| Citation | Kalinichenko VV, et al. (2002) Wild-type levels of the mouse Forkhead Box f1 gene are essential for lung repair. Am J Physiol Lung Cell Mol Physiol 282(6):L1253-65 |
| abstractText | The Forkhead Box (Fox) family of transcription factors plays important roles in regulating expression of genes involved in cellular proliferation and differentiation. In a previous study, we showed that newborn foxf1(+/-) mice with diminished Foxf1 levels exhibited abnormal formation of pulmonary alveoli and capillaries and died postnatally. Interestingly, surviving newborn foxf1(+/-) mice exhibited increased pulmonary Foxf1 levels and normal adult lung morphology, suggesting that wild-type Foxf1 levels are required for lung development and function. The present study was conducted to determine whether adult foxf1(+/-) mice were able to undergo lung repair similar to that observed in wild-type mice. We demonstrated that adult foxf1(+/-) mice died from severe lung hemorrhage after butylated hydroxytoluene (BHT) lung injury and that this phenotype was associated with a 10-fold decrease in pulmonary Foxf1 expression and increased alveolar endothelial cell apoptosis that disrupted capillary integrity. Furthermore, BHT-induced lung hemorrhage of adult foxf1(+/-) mice was associated with a drastic reduction in expression of the Flk-1, bone morphogenetic protein-4, surfactant protein B, platelet endothelial cell adhesion molecule, and vascular endothelial cadherin genes, whereas the expression of these genes was either transiently diminished or increased in wild-type lungs after BHT injury. Because these proteins are critical for lung morphogenesis and endothelial homeostasis, their decreased mRNA levels are likely contributing to BHT-induced lung hemorrhage in foxf1(+/-) mice. Collectively, our data suggest that sustained expression of Foxf1 is essential for normal lung repair and endothelial cell survival in response to pulmonary cell injury. |
