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Semaphorin 3C regulates endothelial cell function by increasing integrin activity
Author(s) -
Banu Nazifa,
Teichman Jason,
DunlapBrown Marya,
Villegas Guillermo,
Tufro Alda
Publication year - 2006
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.05-5698fje
Subject(s) - semaphorin , microbiology and biotechnology , integrin , fibronectin , angiogenesis , cell adhesion , biology , integrin alpha m , extracellular matrix , receptor , cell , cancer research , biochemistry
Class 3 semaphorins (sema 3) are secreted guidance proteins. Sema 3A expressed by endothelial cells controls vascular morphogenesis through integrin inhibition. Sema 3C is required for normal cardiovascular patterning. Here we examined the potential role of sema 3C as regulator of endothelial cell function in vitro using mouse glomerular endothelial cells (MGEC). We determined that MGEC express sema 3C mRNA and protein and its receptors mRNA. Recombinant sema 3C induced MGEC proliferation 18 2% above control, as assessed by bromodeoxyuridine (BrdU) incorporation, and reduced starvation‐induced apoptosis by 46 3%, as indicated by an in situ marker of activated caspase 3. Sema 3C increased MGEC adhesion to fibronectin 79 13% and to collagen 55 12% as compared with control. Sema 3C‐induced MGEC adhesion was prevented by integrin blocking antibodies and involved 1 integrin serine phosphorylation. Sema 3C‐induced MGEC adhesion and proliferation were similar to those induced by vascular endothelial growth factor (VEGF)‐A. Sema 3C induced a 44 11% increase in MGEC directional migration and stimulated MGEC capillary‐like network formation on collagen I gels. Collectively, our data indicate that sema 3C promotes glomerular endothelial cell proliferation, adhesion, directional migration, and tube formation in vitro by stimulating integrin phosphorylation and VEGF 120 secretion, functions that are similar to VEGF‐A and opposite to sema 3A.—Banu, N., Teichman, J., Dunlap‐Brown, M., Villegas, G., Tufro, A. Semaphorin 3C regulates endothelial cell function by increasing integrin activity. FASEB J. 20, E1520 –E1527 (2006)