Ablation of endothelial Pfkfb3 protects mice from acute lung injury in LPS-induced endotoxemia.

ABSTRACT: Acute lung injury (ALI) is one of the leading causes of death in sepsis. Endothelial inflammation and dysfunction play a prominent role in development of ALI. Glycolysis is the predominant bioenergetic pathway for endothelial cells (ECs). However, the role of EC glycolysis in ALI of sepsis remains unclear. Here we show that both the expression and activity of PFKFB3, a key glycolytic activator, were markedly increased in lipopolysaccharide (LPS)-treated human pulmonary arterial ECs (HPAECs) in vitro and in lung ECs of mice challenged with LPS in vivo. PFKFB3 knockdown significantly reduced LPS-enhanced glycolysis in HPAECs. Compared with LPS-challenged wild-type mice, endothelial-specific Pfkfb3 knockout (Pfkfb3^ΔVEC) mice exhibited reduced endothelium permeability, lower pulmona

SUBMITTER: Wang L 

PROVIDER: S-EPMC7310404 | biostudies-literature | 2019 Aug

REPOSITORIES: biostudies-literature