FOSL1 is a novel mediator of endotoxin/lipopolysaccharide-induced pulmonary angiogenic signaling

Bronchopulmonary dysplasia (BPD) is a developmental lung disorder characterized by simplified alveoli and dysmorphic pulmonary vasculature. Recent studies have found that maternal chorioamnionitis increases the incidence of BPD and perinatal mortality, and postnatal sepsis or pneumonia increases the risk of preterm infants developing BPD. Oxygen toxicity and inflammation are both important to the development of BPD, but the mechanistic pathways contributing to aberrant angiogenesis following systemic infection remain unclear. Therefore, the objective of this study was to identify novel pathways by which systemic sepsis programs aberrant angiogenesis in the developing lung using an unbiased approach involving RNA-Seq and bioinformatics methods. By combining RNA sequencing studies in a neonatal mouse model of sterile sepsis followed by validation strategies using genetic manipulation in primary fetal human lung EC and an immortalized lung EC line we developed, we identify the transcription factor FOSL1 (FOS like 1, AP-1 transcription factor subunit), as a novel regulator of endotoxin-mediated aberrant angiogenesis in the lung.