Inactivation of the tyrosine phosphatase SHP-2 drives vascular dysfunction in Sepsis.

ABSTRACT:

Background

Sepsis, the most severe form of infection, involves endothelial dysfunction which contributes to organ failure. To improve therapeutic prospects, elucidation of molecular mechanisms underlying endothelial vascular failure is of essence.

Methods

Polymicrobial contamination induced sepsis mouse model and primary endothelial cells incubated with sepsis serum were used to study SHP-2 in sepsis-induced endothelial inflammation. SHP-2 activity was assessed by dephosphorylation of pNPP, ROS production was measured by DCF oxidation and protein interactions were assessed by proximity ligation assay. Vascular inflammation was studied in the mouse cremaster model and in an in vitro flow assay.

Findings

We identified ROS-dependent inactivation of the tyrosine phosphata

SUBMITTER: Heun Y 

PROVIDER: S-EPMC6491420 | biostudies-literature | 2019 Apr

REPOSITORIES: biostudies-literature