VE-statin, an endothelial repressor of smooth muscle cell migration.
The recruitment and proliferation of smooth muscle cells and pericytes are two key events for the stabilization of newly formed capillaries during angiogenesis and, when out of control in the adult, are the main causes of arteriosclerosis. We have identified a novel gene, named VE-statin for vascular endothelial-statin, which is expressed specifically by endothelial cells of the developing mouse embryo and in the adult, and in early endothelial progenitors. The mouse and human VE-statin genes have been located on chromosome 2 and 9, respectively, they span >10 kbp and are transcribed in two major variants arising from independent initiation sites. The VE-statin transcripts code for a unique protein of 30 kDa that contains a signal peptide and two epidermal growth factor (EGF)-like modules. VE-statin is found in the cellular endoplasmic reticulum and secreted in the cell supernatant. Secreted VE-statin inhibits platelet-derived growth factor (PDGF)-BB-induced smooth muscle cell migration, but has no effects on endothelial cell migration. VE-statin is the first identified inhibitor of mural cell migration specifically produced by endothelial cells.
Soncin
Fabrice
F
CNRS UMR 8526, Institut de Biologie de Lille, 1 rue Calmette, 59021 Lille Cedex, France. fabrice.soncin@ibl.fr
Mattot
Virginie
V
Lionneton
Frédéric
F
Spruyt
Nathalie
N
Lepretre
Frédéric
F
Begue
Agnès
A
Stehelin
Dominique
D
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002135:Calcium-Binding Proteins; D002455:Cell Division; D002460:Cell Line; D002465:Cell Movement; D002478:Cells, Cultured; D002899:Chromosomes, Human, Pair 9 / Q000235:genetics; D003001:Cloning, Molecular; D018076:DNA, Complementary / Q000235:genetics; D004268:DNA-Binding Proteins; D066255:EGF Family of Proteins; D016228:Endothelial Growth Factors / Q000235:genetics / Q000502:physiology*; D004730:Endothelium, Vascular / Q000254:growth & development / Q000502:physiology*; D006131:Growth Inhibitors / Q000235:genetics / Q000502:physiology*; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D066298:In Vitro Techniques; D051741:Kruppel-Like Transcription Factors; D051379:Mice; D008969:Molecular Sequence Data; D009131:Muscle, Smooth, Vascular / Q000166:cytology* / Q000254:growth & development / Q000502:physiology; D018919:Neovascularization, Physiologic; D011506:Proteins / Q000235:genetics / Q000502:physiology*; D014157:Transcription Factors / Q000235:genetics / Q000502:physiology*
D002135:Calcium-Binding Proteins; D018076:DNA, Complementary; D004268:DNA-Binding Proteins; D066255:EGF Family of Proteins; C527877:EGFL7 protein, human; C479627:Egfl7 protein, mouse; D016228:Endothelial Growth Factors; D006131:Growth Inhibitors; D051741:Kruppel-Like Transcription Factors; D011506:Proteins; D014157:Transcription Factors; C117684:Vezf1 protein, mouse