A new study uncovers a transcriptional pathway that is critical for recovery from acute lung injury, opening the door to developing therapies targeting this pathway.
The endothelial cells lining blood vessels in the lungs act as a barrier between the external environment and the blood. Acute lung injury caused by disease, infection, or trauma impairs this barrier function of the endothelium, resulting in the buildup of fluid in the lungs, known as pulmonary edema, and inflammation. Complications arising from acute lung injury can require hospitalization and can be fatal.
Here, Yuqi Cai and colleagues investigated FOXF1, a transcription factor known to promote the formation of blood vessels in the developing lungs. They found that inducible loss of the gene encoding FOXF1 in lung endothelial cells in adult mice caused the mice to die from respiratory problems, pulmonary edema, and lung inflammation. Even adult mice that lacked only one Foxf1 allele in lu ng endothelial cells were more susceptible to acute lung injury. Furthermore, the researchers found that FOXF1 transcriptionally activated a gene encoding the receptor for S1P, a lipid mediator found in the circulation that enhances the barrier function of endothelial cells.
This finding explains why FOXF1 was so critical in preventing lung edema and in spurring recovery from lung injury. By promoting the production of the receptor for S1P, FOXF1 stabilized or restored endothelial barrier function. Altogether, the results raise the possibility of developing therapies that boost FOXF1 activity or S1P signaling to treat acute lung injury.