Which are observed in both animal models as well as human infant studies. Furthermore, the fact that hyperoxia exposure led to a decrease in VEGF-A, a critical factor for angiogenesis, concurs with the current understanding that this protein is critical for normal alveoli development. Our finding of a significant decrease in TGFb2 with hyperoxia exposure as well as the other signaling proteins important in the TGF-BMP-Smad pathway is in contrast to some studies of neonatal hyperoxia-induced lung injury where an elevation of TGF-b isoforms are seen with hyperoxia exposure. There are a couple of possible explanations for this discrepancy. First, many studies measured only TGFb1, the predominant isoform, and although we saw a lowering in gene expression with hyperoxia, it was not statistically different from the control or normoxia group. Our hyperoxia model is of 10-day duration and longer durations of hyperoxia exposure may be needed to see a change in TGFb1. It is possible that there is a biphasic change in TGFb isoforms similar to VEGF where a decrease is observed early in the course of disease evolution and this is followed by a later increase. Little data exists to the timing and changes seen in TGFb2 gene expression with hyperoxia and its specific role in lung development. However, our finding of decreased expression of TGFb2 and Smad 3 with hyperoxia and concomitantly alveolar simplification and, in contrast, an increase in TGFb2 and Smad 3 in the LXA4 and combination groups with parallel improved alveolarization is consistent with scientific literature examining the complex role of TGFb isoforms in lung development. This duality of TGFb function in lung development under different conditions is supported by Vincencio et al. demonstrating that TGFb can induce changes of BPD when over expressed between postnatal days P7 and P14 in a murine model. Yet in contrast, knockout mouse models of Smad3 overlapping with this time period indicate that the TGFb/Smad3 signaling pathway can beneficially induce alveolarization. Thus the timing of the change in TGFb and Smad3 expression relative to the period in lung development may be the defining factor as to whether it inhibits or promotes airway maturation. However, although some aspects may be shared in the pathophysiology of adult and neonatal lung injury, the neonate, especially the preterm infant, is unique in that lung development is still ongoing and the compromise in normal developmental processes also contributes to the specific features in neonatal lung injury. Our date indicate that RvD1 impacted the expression of genes for both inflammation and the extracellular matrix biomarker, both of which may have contributed to reducing septal wall thickness. RvD1 did not have a substantial effect alone on VEGF-A or the other growth factor biomarkers in the TGFb family. Nor did RvD1 impact the expression of the BMP-Smad signaling proteins.