The Glycolysis Regulatory Enzyme PFK-FB3 Enhances Endothelial Barrier Restoration in Acute Lung Injury

Acute lung injury (ALI) is a devastating inflammatory complication of infectious lung disease, characterized by a breakdown of the pulmonary vascular barrier and the subsequent formation of protein-rich alveolar edema. In recent years, considerable advances have been made in the understanding of how intracellular signaling regulates the disruption and re-assembly of adherens junctions (AJs) which are mediators of the endothelial barrier function. Little is known about the role of endothelial metabolism as a modulator of endothelial barrier function and its restoration in the setting of lung vascular injury. We hypothesized that the glycolysis regulatory enzyme PFK-FB3 would support re-annealing of the endothelial barrier because glycolysis allows for the local generation of ATP at the AJs. We observed a 2–3-fold upregulation of PFK-FB3, an enzyme which is a critical regulator of glycolytic activity, in response to inflammatory injury in human lung endothelial cells (p<0.05). ATP levels also increased at t...