The endocrine-gland-derived VEGF homologue Bv8 promotes angiogenesis in the testis: Localization of Bv8 receptors to endothelial cells.
We recently identified an angiogenic mitogen, endocrine-gland-derived vascular endothelial growth factor (EG-VEGF), with selective activity for endothelial cells of endocrine tissues. Here we describe the characterization of a highly related molecule, Bv8, also known as prokineticin-2. Human Bv8 shares 60% identity and 75% similarity with EG-VEGF. The human and mouse Bv8 genes share a common structure. Like EG-VEGF, Bv8 is able to induce proliferation, survival and migration of adrenal cortical capillary endothelial cells. Bv8 gene expression is induced by hypoxic stress. Bv8 expression occurs predominantly in the testis and is largely restricted to primary spermatocytes. Adenoviral delivery of Bv8 or EG-VEGF to the mouse testis resulted in a potent angiogenic response. We have localized the expression of the Bv8EG-VEGF receptors within the testis to vascular endothelial cells. The testis exhibits relatively high turnover of endothelial cells. Therefore, Bv8 and EG-VEGF, along with other factors such as VEGF-A, may maintain the integrity and also regulate proliferation of the blood vessels in the testis.
LeCouter
Jennifer
J
Department of Molecular Oncology, Genentech, Inc., South San Francisco, CA 94080, USA.
Lin
Rui
R
Tejada
Max
M
Frantz
Gretchen
G
Peale
Franklin
F
Hillan
Kenneth J
KJ
Ferrara
Napoleone
N
D000256:Adenoviridae / Q000235:genetics; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002417:Cattle; D002455:Cell Division; D002465:Cell Movement; D002478:Cells, Cultured; D002633:Chemotaxis; D018076:DNA, Complementary / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D016228:Endothelial Growth Factors / Q000378:metabolism; D004727:Endothelium / Q000378:metabolism; D004730:Endothelium, Vascular / Q000166:cytology; D005768:Gastrointestinal Hormones / Q000378:metabolism* / Q000502:physiology*; D006801:Humans; D000860:Hypoxia; D015151:Immunoblotting; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism; D008222:Lymphokines / Q000378:metabolism; D008297:Male; D051379:Mice; D008957:Models, Genetic; D008969:Molecular Sequence Data; D009389:Neovascularization, Pathologic; D009479:Neuropeptides; D020033:Protein Isoforms; D012313:RNA / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D043562:Receptors, G-Protein-Coupled; D018000:Receptors, Peptide / Q000096:biosynthesis*; D011994:Recombinant Proteins / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D013094:Spermatozoa / Q000166:cytology; D013737:Testis / Q000098:blood supply / Q000378:metabolism / Q000473:pathology; D014018:Tissue Distribution; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
D018076:DNA, Complementary; D016228:Endothelial Growth Factors; D005768:Gastrointestinal Hormones; D036341:Intercellular Signaling Peptides and Proteins; D008222:Lymphokines; D009479:Neuropeptides; C423608:PROK2 protein, human; C470838:PROKR2 protein, human; C486586:Prok2 protein, mouse; D020033:Protein Isoforms; D012333:RNA, Messenger; D043562:Receptors, G-Protein-Coupled; D018000:Receptors, Peptide; D011994:Recombinant Proteins; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D012313:RNA