Poldip2 Deficiency Protects Against Lung Edema and Vascular Inflammation in a Model of Acute Respiratory Distress Syndrome

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 delta-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 hours, lung inflammatory signaling and leukocyte infiltration. Moreover, reduced Poldip2 suppressed LPS-induced 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.

Source: Clinical Science - January 8, 2019 Category: Biomedical Science Authors: Forrester, S. J., Xu, Q., Kikuchi, D. S., Okwan-Duodu, D., Campos, A. C., Faidley, E. A., Zhang, G., Lassegue, B., Sadikot, R. T., Griendling, K. K., Hernandes, M. S. Tags: PublishAheadOfPrint Source Type: research