10.25376/hra.7971245.v1 Steven J. Forrester Steven J. Forrester Qian Xu Qian Xu Daniel Kikuchi Daniel Kikuchi Derick Okwan-Duodu Derick Okwan-Duodu Ana Carolina Campos Ana Carolina Campos Elizabeth Faidley Elizabeth Faidley Guogang Zhang Guogang Zhang Bernard Lassègue Bernard Lassègue Ruxana T. Sadikot Ruxana T. Sadikot Kathy K. Griendling Kathy K. Griendling Marina S. Hernandes Marina S. Hernandes Supplemental 1.pdf Health Research Alliance 2019 Poldip2; acute respiratory distress syndrome; inflammation; leukocyte Animal Physiology - Systems Cell Biology 2019-04-09 15:49:29 Figure https://hra.figshare.com/articles/figure/Supplemental_1_pdf/7971245 <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>