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Supplemental 1.pdf

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posted on 2019-04-09, 15:49 authored by Steven J. Forrester, Qian Xu, Daniel Kikuchi, Derick Okwan-Duodu, Ana Carolina Campos, Elizabeth Faidley, Guogang Zhang, Bernard Lassègue, Ruxana T. Sadikot, Kathy K. Griendling, Marina S. Hernandes
Acute respiratory distress syndrome (ARDS) in a deadly disease that can be brought on
by endotoxins such as lipopolysaccharide (LPS). ARDS is characterized by vascular permeability,
a severe inflammatory response, lung leukocyte infiltration, and resultant lung
edema. Polymerase δ-interacting protein 2 (Poldip2) is a novel regulator of blood–brain barrier
permeability; however, its role in regulating lung permeability and vascular inflammation
is unknown. Here, the role of Poldip2 in regulating vascular permeability and inflammation
in a mouse model of ARDS was assessed. Heterozygous deletion of Poldip2 was
found to reduce LPS-induced mortality within 20 h, lung inflammatory signaling, and leukocyte
infiltration. Moreover, reduced Poldip2-suppressed LP-induced vascular cell adhesion
molecule (VCAM)-1 induction, leukocyte recruitment, and mitochondrial reactive oxygen
species (ROS) production in vitro. These data indicate that Poldip2 is an important regulator
of the debilitating consequences of ARDS, potentially through the regulation of mitochondrial
ROS-induced inflammatory signaling. Consequently, inhibition of Poldip2 may be
a viable option for therapeutic discovery moving forward.


Grant ID

American Heart Association 17SDG33410777

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