Forrester Clinical Science 2019.pdf
Acute respiratory distress syndrome (ARDS) in a deadly disease that can be brought onby endotoxins such as lipopolysaccharide (LPS). ARDS is characterized by vascular permeability,a severe inflammatory response, lung leukocyte infiltration, and resultant lungedema. Polymerase δ-interacting protein 2 (Poldip2) is a novel regulator of blood–brain barrierpermeability; however, its role in regulating lung permeability and vascular inflammationis unknown. Here, the role of Poldip2 in regulating
... lar permeability and inflammationin a mouse model of ARDS was assessed. Heterozygous deletion of Poldip2 wasfound to reduce LPS-induced mortality within 20 h, lung inflammatory signaling, and leukocyteinfiltration. Moreover, reduced Poldip2-suppressed LP-induced vascular cell adhesionmolecule (VCAM)-1 induction, leukocyte recruitment, and mitochondrial reactive oxygenspecies (ROS) production in vitro. These data indicate that Poldip2 is an important regulatorof the debilitating consequences of ARDS, potentially through the regulation of mitochondrialROS-induced inflammatory signaling. Consequently, inhibition of Poldip2 may bea viable option for therapeutic discovery moving forward.