Increased basal fibronectin is sufficient to promote excess endothelial cell matrix assembly causing localized...

Area of Science:

• Vascular Biology
• Extracellular Matrix Biology
• Cellular Physiology

Background:

• The subendothelial extracellular matrix (ECM) regulates endothelial cell (EC) behavior.
• Fibronectin (FN), an ECM protein, is scarce in healthy vessels but increases in disease, correlating with endothelial dysfunction.

Purpose of the Study:

• To investigate the causal role of excessive fibronectin matrix assembly in disrupting endothelial cell functions and barrier integrity.

Main Methods:

• Mimicked increased fibronectin expression by adding exogenous FN to the basal side of Transwell inserts.
• Analyzed dose-dependent fibronectin matrix assembly and its correlation with EC morphology, VE-cadherin junctions, cell cycle, and barrier permeability.
• Assessed tumor cell adhesion to the endothelial monolayer.

Main Results:

• Exogenous FN dose-dependently increased subendothelial FN matrix assembly.
• Regional increases in FN matrix correlated with disrupted EC morphology, VE-cadherin junctions, and cell cycle.
• Increased FN matrix preceded endothelial monolayer disorganization and leakiness, enhancing tumor cell adhesion.

Conclusions:

• Subendothelial fibronectin matrix accumulation is a causative factor in endothelial monolayer disorganization and leakiness.
• Regulating fibronectin accumulation presents a potential therapeutic target for controlling fibrosis and related diseases.