Semaphorin 3C regulates endothelial cell function by increasing integrin activity

Area of Science:

• Cell Biology
• Developmental Biology
• Molecular Biology

Background:

• Class 3 semaphorins (Sema 3) are secreted guidance proteins involved in development.
• Sema 3A regulates vascular morphogenesis by inhibiting integrins.
• Sema 3C is crucial for cardiovascular patterning.

Purpose of the Study:

• To investigate the role of Sema 3C in regulating mouse glomerular endothelial cell (MGEC) function in vitro.
• To determine if Sema 3C influences MGEC proliferation, apoptosis, adhesion, migration, and tube formation.

Main Methods:

• MGEC were treated with recombinant Sema 3C.
• Cell proliferation was assessed using bromodeoxyuridine (BrdU) incorporation.
• Apoptosis was measured via activated caspase 3.
• Cell adhesion, migration, and capillary-like network formation were quantified.
• Integrin involvement was studied using blocking antibodies and assessing beta1 integrin serine phosphorylation.

Main Results:

• MGEC express Sema 3C and its receptors.
• Sema 3C significantly increased MGEC proliferation, adhesion to fibronectin and collagen, and directional migration.
• Sema 3C reduced starvation-induced apoptosis.
• Sema 3C promoted capillary-like tube formation.
• Sema 3C's effects on adhesion and proliferation were comparable to VEGF-A and involved beta1 integrin phosphorylation.

Conclusions:

• Sema 3C promotes key endothelial cell functions: proliferation, adhesion, migration, and tube formation.
• These pro-angiogenic effects are mediated by integrin phosphorylation and are distinct from Sema 3A's inhibitory role.
• Sema 3C acts similarly to VEGF-A in promoting endothelial cell activity.