Focal adhesion kinase and Src mediate microvascular hyperpermeability caused by fibrinogen- γC- terminal fragments.

ABSTRACT:

Objectives

We previously reported microvascular leakage resulting from fibrinogen-γ chain C-terminal products (γC) occurred via a RhoA-dependent mechanism. The objective of this study was to further elucidate the signaling mechanism by which γC induces endothelial hyperpermeability. Since it is known that γC binds and activates endothelial αvβ3, a transmembrane integrin receptor involved in intracellular signaling mediated by the tyrosine kinases FAK and Src, we hypothesized that γC alters endothelial barrier function by activating the FAK-Src pathway leading to junction dissociation and RhoA driven cytoskeletal stress-fiber formation.

Methods and results

Using intravital microscopy of rat mesenteric microvessels, we show increased extravasation of plasma protein (albumin) r

SUBMITTER: Guo X 

PROVIDER: S-EPMC7192500 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature