Supplemental 1.pdf

<div>Acute respiratory distress syndrome (ARDS) in a deadly disease that can be brought on</div><div>by endotoxins such as lipopolysaccharide (LPS). ARDS is characterized by vascular permeability,</div><div>a severe inflammatory response, lung leukocyte infiltration, and resultant lung</div><div>edema. Polymerase δ-interacting protein 2 (Poldip2) is a novel regulator of blood–brain barrier</div><div>permeability; however, its role in regulating lung permeability and vascular inflammation</div><div>is unknown. Here, the role of Poldip2 in regulating vascular permeability and inflammation</div><div>in a mouse model of ARDS was assessed. Heterozygous deletion of Poldip2 was</div><div>found to reduce LPS-induced mortality within 20 h, lung inflammatory signaling, and leukocyte</div><div>infiltration. Moreover, reduced Poldip2-suppressed LP-induced vascular cell adhesion</div><div>molecule (VCAM)-1 induction, leukocyte recruitment, and mitochondrial reactive oxygen</div><div>species (ROS) production in vitro. These data indicate that Poldip2 is an important regulator</div><div>of the debilitating consequences of ARDS, potentially through the regulation of mitochondrial</div><div>ROS-induced inflammatory signaling. Consequently, inhibition of Poldip2 may be</div><div>a viable option for therapeutic discovery moving forward.</div>