Identification of an angiogenic mitogen selective for endocrine gland endothelium.
The known endothelial mitogens stimulate growth of vascular endothelial cells without regard to their tissue of origin. Here we report a growth factor that is expressed largely in one type of tissue and acts selectively on one type of endothelium. This molecule, called endocrine-gland-derived vascular endothelial growth factor (EG-VEGF), induced proliferation, migration and fenestration (the formation of membrane discontinuities) in capillary endothelial cells derived from endocrine glands. However, EG-VEGF had little or no effect on a variety of other endothelial and non-endothelial cell types tested. Similar to VEGF, EG-VEGF possesses a HIF-1 binding site, and its expression is induced by hypoxia. Both EG-VEGF and VEGF resulted in extensive angiogenesis and cyst formation when delivered in the ovary. However, unlike VEGF, EG-VEGF failed to promote angiogenesis in the cornea or skeletal muscle. Expression of human EG-VEGF messenger RNA is restricted to the steroidogenic glands, ovary, testis, adrenal and placenta and is often complementary to the expression of VEGF, suggesting that these molecules function in a coordinated manner. EG-VEGF is an example of a class of highly specific mitogens that act to regulate proliferation and differentiation of the vascular endothelium in a tissue-specific manner.
LeCouter
J
J
Department of Molecular Oncology, Genentech Inc., South San Francisco, CA 94080, USA.
Kowalski
J
J
Foster
J
J
Hass
P
P
Zhang
Z
Z
Dillard-Telm
L
L
Frantz
G
G
Rangell
L
L
DeGuzman
L
L
Keller
G A
GA
Peale
F
F
Gurney
A
A
Hillan
K J
KJ
Ferrara
N
N
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002417:Cattle; D015687:Cell Hypoxia; D002478:Cells, Cultured; D018076:DNA, Complementary; D004195:Disease Models, Animal; D004702:Endocrine Glands / Q000502:physiology*; D016228:Endothelial Growth Factors / Q000502:physiology; D004730:Endothelium, Vascular / Q000502:physiology*; D005260:Female; D005768:Gastrointestinal Hormones; D005786:Gene Expression Regulation; D006801:Humans; D008222:Lymphokines / Q000502:physiology; D051379:Mice; D008819:Mice, Nude; D008934:Mitogens / Q000235:genetics / Q000302:isolation & purification* / Q000502:physiology; D008969:Molecular Sequence Data; D018919:Neovascularization, Physiologic; D010048:Ovarian Cysts / Q000209:etiology; D051381:Rats; D011993:Recombinant Fusion Proteins; D017386:Sequence Homology, Amino Acid; D014018:Tissue Distribution; D042461:Vascular Endothelial Growth Factor A; D042662:Vascular Endothelial Growth Factor, Endocrine-Gland-Derived; D042442:Vascular Endothelial Growth Factors
D018076:DNA, Complementary; D016228:Endothelial Growth Factors; D005768:Gastrointestinal Hormones; D008222:Lymphokines; D008934:Mitogens; C467610:PROK1 protein, human; D011993:Recombinant Fusion Proteins; D042461:Vascular Endothelial Growth Factor A; D042662:Vascular Endothelial Growth Factor, Endocrine-Gland-Derived; D042442:Vascular Endothelial Growth Factors