Differential Endothelial Transcriptomics Identifies Semaphorin 3G as a Vascular Class 3 Semaphorin

• Published in: Arteriosclerosis, thrombosis, and vascular biology Vol. 31; no. 1; pp. 151 - 159
• Main Authors: Kutschera, Simone, Weber, Holger, Weick, Anja, De Smet, Frederik, Genove, Guillem, Takemoto, Minoru, Prahst, Claudia, Riedel, Maria, Mikelis, Constantinos, Baulande, Sylvain, Champseix, Catherine, Kummerer, Petra, Conseiller, Emmanuel, Multon, Marie-Christine, Heroult, Melanie, Bicknell, Roy, Carmeliet, Peter, Betsholtz, Christer, Augustin, Hellmut G
• Format: Journal Article
• Language: English
• Published: Philadelphia, PA American Heart Association, Inc 01.01.2011; Lippincott Williams & Wilkins
• Subjects: Animals; Atherosclerosis (general aspects, experimental research); Autocrine Communication; Biological and medical sciences; Blood and lymphatic vessels; Blood vessels and receptors; C-Reactive Protein - metabolism; Cardiology. Vascular system; Cells, Cultured; Coculture Techniques; Diseases of the peripheral vessels. Diseases of the vena cava. Miscellaneous; Endothelial Cells - metabolism; Endothelium, Vascular - embryology; Endothelium, Vascular - metabolism; Fundamental and applied biological sciences. Psychology; Gene Expression Profiling - methods; Gene Expression Regulation, Developmental; Genotype; Humans; Medical sciences; Medicin och hälsovetenskap; Mice; Mice, 129 Strain; Mice, Inbred C57BL; Mice, Knockout; Muscle, Smooth, Vascular - embryology; Muscle, Smooth, Vascular - metabolism; Myocytes, Smooth Muscle - metabolism; Neovascularization, Physiologic; Nerve Tissue Proteins - metabolism; Oligonucleotide Array Sequence Analysis; Paracrine Communication; Phenotype; Protein Binding; Protein Processing, Post-Translational; Recombinant Proteins - metabolism; RNA Interference; Semaphorins - deficiency; Semaphorins - genetics; Semaphorins - metabolism; Transfection; Vertebrates: cardiovascular system; Zebrafish - genetics; Zebrafish - metabolism; Zebrafish Proteins - genetics; Zebrafish Proteins - metabolism; Vascular disease; semaphorin; Angiogenesis; Endothelial cell; smooth muscle cell; Atherosclerosis; Smooth muscle; Cardiovascular disease; neuropilin
• ISSN: 1079-5642; 1524-4636; 1524-4636
• DOI: 10.1161/ATVBAHA.110.215871

OBJECTIVE—To characterize the role of a vascular-expressed class 3 semaphorin (semaphorin 3G [Sema3G]). METHODS AND 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. CONCLUSION—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.