title: CREG1 promotes angiogenesis and neovascularization.
abstract: Angiogenesis has long been considered as an important strategy for ischemic injury. It has been reported that cellular repressor of E1A-stimulated genes (CREG1) promotes human umbilical vein endothelial cell (HUVEC) proliferation, migration, and protects endothelial cell (EC) from apoptosis. However, its potential effect on angiogenesis remains undefined. In the present study, we investigated the role and mechanisms of CREG1 in promoting angiogenesis. We found that adenovirus-transduced CREG1 expression in HUVECs increases EC tube formation in matrigel and promotes neovascularization in matrigel plugs grafted into wild type mice. In addition, adenoviral CREG1 expression enhances filopodia formation, which is accompanied by increased expression of integrin-linked kinase (ILK) and activation of its downstream effector Cdc42. Hindlimb perfusion was significantly reduced after femoral artery ligation in CREG1 heterozygous knockout mice. Finally, adenoviral CREG1 was injected intramuscularly in gastrochemius and partially restores ischemic hindlimb perfusion. Our results demonstrated that CREG1 increases EC filopodia formation and vascular assembly via ILK-Cdc42 activation and promotes neovascularization, which might be a therapeutic target for ischemic injury.
authors.forename: Chenghui
authors.initials: C
authors.lastname: Yan
authors.forename: Pu
authors.initials: P
authors.lastname: Fang
authors.forename: Huimin
authors.initials: H
authors.lastname: Zhang
authors.forename: Jie
authors.initials: J
authors.lastname: Tao
authors.forename: Xiaoxiang
authors.initials: X
authors.lastname: Tian
authors.forename: Yang
authors.initials: Y
authors.lastname: Li
authors.forename: Jian
authors.initials: J
authors.lastname: Zhang
authors.forename: Mingyu
authors.initials: M
authors.lastname: Sun
authors.forename: Shaohua
authors.initials: S
authors.lastname: Li
authors.forename: Hong
authors.initials: H
authors.lastname: Wang
authors.forename: Yaling
authors.initials: Y
authors.lastname: Han
mesh_terms: D000818:Animals; D001808:Blood Vessels / Q000378:metabolism; D015153:Blotting, Western; D002478:Cells, Cultured; D003094:Collagen; D004338:Drug Combinations; D042783:Endothelial Cells / Q000378:metabolism / Q000637:transplantation; D057809:HEK293 Cells; D006614:Hindlimb / Q000098:blood supply / Q000378:metabolism; D061307:Human Umbilical Vein Endothelial Cells / Q000378:metabolism*; D006801:Humans; D007511:Ischemia / Q000503:physiopathology; D007797:Laminin; D008297:Male; D057507:Mice, 129 Strain; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D018919:Neovascularization, Physiologic / Q000235:genetics / Q000502:physiology*; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism; D011509:Proteoglycans; D011554:Pseudopodia / Q000235:genetics / Q000502:physiology*; D034622:RNA Interference; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D020764:cdc42 GTP-Binding Protein / Q000235:genetics / Q000378:metabolism; D000099200:Scaffold Protein ILK
chemical_list: D003094:Collagen; D004338:Drug Combinations; D007797:Laminin; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D017346:Protein Serine-Threonine Kinases; D011509:Proteoglycans; D012097:Repressor Proteins; D020764:cdc42 GTP-Binding Protein; D000099200:Scaffold Protein ILK; C114068:CREG1 protein, human; C059485:matrigel