Mouse endocrine gland-derived vascular endothelial growth factor: a distinct expression pattern from its human ortholog suggests different roles as a regulator of organ-specific angiogenesis.
We recently described human endocrine gland-derived vascular endothelial growth factor (EG-VEGF) as an endothelial cell mitogen with a novel selective activity and an expression pattern essentially limited to steroidogenic glands. Herein we present the identification and characterization of the mouse ortholog. The mouse cDNA and predicted amino acid sequences are, respectively, 86% and 88% identical with the human. Surprisingly, the mouse EG-VEGF transcript is predominantly expressed in liver and kidney. A comparison of human and mouse EG-VEGF promoter sequences revealed a potential binding site for NR5A1, which is known to be a pivotal element for steroidogenic-specific transcription, in the human but not mouse promoter. In situ hybridization studies localized expression of mouse EG-VEGF mRNA to hepatocytes and renal tubule cells. Interestingly, capillary endothelial cells in these sites share several common structural features with those found in steroidogenic glands. Within liver and kidney, EG-VEGF receptor expression was largely restricted to endothelial cells. Mouse EG-VEGF promoted proliferation and survival of endothelial cells. We propose that mouse EG-VEGF, like human EG-VEGF, plays a role in regulating the phenotype and growth properties of endothelial cells within distinct capillary beds.
Department of Molecular Oncology, Genentech Inc., South San Francisco, California 94080, USA.
Jennifer
J
LeCouter
Rui
R
Lin
Gretchen
G
Frantz
Zemin
Z
Zhang
Kenneth
K
Hillan
Napoleone
N
Ferrara
D043925:Angiogenesis Inducing Agents / Q000235:genetics*; D000818:Animals; D002470:Cell Survival / Q000502:physiology; D002874:Chromosome Mapping; D018076:DNA, Complementary; D004702:Endocrine Glands / Q000502:physiology; D004730:Endothelium, Vascular / Q000737:chemistry / Q000166:cytology / Q000502:physiology*; D005768:Gastrointestinal Hormones / Q000235:genetics*; D018507:Gene Expression Regulation, Developmental; D017403:In Situ Hybridization; D007668:Kidney / Q000098:blood supply; D008099:Liver / Q000098:blood supply; D051379:Mice; D008934:Mitogens / Q000235:genetics; D008969:Molecular Sequence Data; D018919:Neovascularization, Physiologic / Q000502:physiology*; D009479:Neuropeptides; D011401:Promoter Regions, Genetic / Q000235:genetics; D012333:RNA, Messenger / Q000032:analysis; D040262:Receptors, Vascular Endothelial Growth Factor / Q000032:analysis; D017386:Sequence Homology, Amino Acid; D012689:Sequence Homology, Nucleic Acid; D013045:Species Specificity; D042461:Vascular Endothelial Growth Factor A; D042662:Vascular Endothelial Growth Factor, Endocrine-Gland-Derived
D043925:Angiogenesis Inducing Agents; D018076:DNA, Complementary; D005768:Gastrointestinal Hormones; D008934:Mitogens; D009479:Neuropeptides; C467610:PROK1 protein, human; C486586:Prok2 protein, mouse; D012333:RNA, Messenger; D042461:Vascular Endothelial Growth Factor A; D042662:Vascular Endothelial Growth Factor, Endocrine-Gland-Derived; C467480:vascular endothelial growth factor A, mouse; D040262:Receptors, Vascular Endothelial Growth Factor