Differential endothelial transcriptomics identifies semaphorin 3G as a vascular class 3 semaphorin.
OBJECTIVE
To characterize the role of a vascular-expressed class 3 semaphorin (semaphorin 3G [Sema3G]).


RESULTS
Semaphorins have been identified as axon guidance molecules. Yet, they have more recently also been characterized as attractive and repulsive regulators of angiogenesis. Through a transcriptomic screen, we identified Sema3G as a molecule of angiogenic endothelial cells. Sema3G-deficient mice are viable and exhibit no overt vascular phenotype. Yet, LacZ expression in the Sema3G locus revealed intense arterial vascular staining in the angiogenic vasculature, starting at E9.5, which was detectable throughout adolescence and downregulated in adult vasculature. Sema3G is expressed as a full-length 100-kDa secreted molecule that is processed by furin proteases to yield 95- and a 65-kDa Sema domain-containing subunits. Full-length Sema3G binds to NP2, whereas processed Sema3G binds to NP1 and NP2. Expression profiling and cellular experiments identified autocrine effects of Sema3G on endothelial cells and paracrine effects on smooth muscle cells.


CONCLUSIONS
Although the mouse knockout phenotype suggests compensatory mechanisms, the experiments identify Sema3G as a primarily endothelial cell-expressed class 3 semaphorin that controls endothelial and smooth muscle cell functions in autocrine and paracrine manners, respectively.
Vascular Oncology and Metastasis, German Cancer Research Center Heidelberg, Im Neuenheimer Feld 280, Heidelberg, Germany.
Simone
S
Kutschera
Holger
H
Weber
Anja
A
Weick
Frederik
F
De Smet
Guillem
G
Genove
Minoru
M
Takemoto
Claudia
C
Prahst
Maria
M
Riedel
Constantinos
C
Mikelis
Sylvain
S
Baulande
Catherine
C
Champseix
Petra
P
Kummerer
Emmanuel
E
Conseiller
Marie-Christine
MC
Multon
Melanie
M
Heroult
Roy
R
Bicknell
Peter
P
Carmeliet
Christer
C
Betsholtz
Hellmut G
HG
Augustin
D000818:Animals; D019898:Autocrine Communication; D002097:C-Reactive Protein / Q000378:metabolism; D002478:Cells, Cultured; D018920:Coculture Techniques; D042783:Endothelial Cells / Q000378:metabolism*; D004730:Endothelium, Vascular / Q000196:embryology / Q000378:metabolism*; D020869:Gene Expression Profiling / Q000379:methods; D018507:Gene Expression Regulation, Developmental; D005838:Genotype; D006801:Humans; D051379:Mice; D057507:Mice, 129 Strain; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009131:Muscle, Smooth, Vascular / Q000196:embryology / Q000378:metabolism; D032389:Myocytes, Smooth Muscle / Q000378:metabolism; D018919:Neovascularization, Physiologic; D009419:Nerve Tissue Proteins / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D019899:Paracrine Communication; D010641:Phenotype; D011485:Protein Binding; D011499:Protein Processing, Post-Translational; D034622:RNA Interference; D011994:Recombinant Proteins / Q000378:metabolism; D039961:Semaphorins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D014162:Transfection; D015027:Zebrafish / Q000235:genetics / Q000378:metabolism; D029961:Zebrafish Proteins / Q000235:genetics / Q000378:metabolism; D000099153:Pentraxins
D002097:C-Reactive Protein; D009419:Nerve Tissue Proteins; D011994:Recombinant Proteins; D039961:Semaphorins; D029961:Zebrafish Proteins; D000099153:Pentraxins; C505763:semaphorin 3G, mouse