Axon Guidance-Related Factor FLRT3 Regulates VEGF-Signaling and Endothelial Cell Function

Area of Science:

• Cell Biology
• Neuroscience
• Angiogenesis Research

Background:

• Vascular endothelial growth factors (VEGFs) are crucial for endothelial cell (EC) function in angiogenesis.
• Axon guidance factors are increasingly recognized for their roles in vascular patterning and angiogenesis.

Purpose of the Study:

• To investigate the role of fibronectin and leucine-rich transmembrane protein-3 (FLRT3), an axon guidance factor, in endothelial cells.
• To determine FLRT3's involvement in VEGF signaling pathways and its impact on EC function.

Main Methods:

• Upregulation of FLRT3 in ECs following VEGF stimulation.
• Analysis of FLRT3 transcriptional regulation, focusing on transcriptional elongation.
• Utilized siRNA to block FLRT3 function and assessed effects on EC survival, migration, and tube formation.

Main Results:

• FLRT3 expression is transcriptionally paused in non-stimulated ECs and rapidly upregulated upon VEGF stimulation.
• FLRT3 knockdown reduced EC survival and capillary-like structure formation but enhanced migration and wound closure.
• FLRT3 exhibits a dual role in ECs, influencing survival, migration, and tube formation.

Conclusions:

• FLRT3 has a novel function in endothelial cells, participating in VEGF-stimulated EC survival, migration, and tube formation.
• FLRT3 is identified as a new player among axon guidance-related factors involved in VEGF signaling and EC regulation.
• Findings suggest FLRT3's bifunctional signaling capacity extends to vascular biology.