Poldip2 deficiency protects against lung edema and vascular inflammation in a model of acute respiratory distress syndrome

Steven J. Forrester, Qian Xu, Daniel S. Kikuchi, Derick Okwan-Duodu, Ana Carolina Campos, Elizabeth A. Faidley, Guogang Zhang, Bernard Lassègue, Ruxana T. Sadikot, Kathy K. Griendling, Marina S. Hernandes

Research output: Contribution to journalArticlepeer-review

4 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)321-334
Number of pages14
JournalClinical Science
Volume133
Issue number2
DOIs
StatePublished - Jan 1 2019
Externally publishedYes

ASJC Scopus subject areas

  • Medicine(all)

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