Adenovirus-mediated E2-EPF UCP gene transfer prevents autoamputation in a mouse model of hindlimb ischemia

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dc.contributor.authorJung Hwa Lim-
dc.contributor.authorHyo-Jung Shin-
dc.contributor.authorKyeong Su Park-
dc.contributor.authorC H Lee-
dc.contributor.authorCho-Rok Jung-
dc.contributor.authorDong Soo Im-
dc.description.abstractE2-EPF ubiquitin carrier protein (UCP) stabilizes hypoxia-inducible factor-1α (HIF-1α) inducing ischemic vascular responses. Here, we investigated the effect of UCP gene transfer on therapeutic angiogenesis. Adenovirus-encoded UCP (Ad-F-UCP) increased the expression of vascular endothelial growth factor (VEGF) and fibroblast growth factor-2 (FGF-2) in cells and mice. Conditioned media from UCP-overexpressing cells promoted proliferation, tubule formation, and invasion of human umbilical-vascular- endothelial cells (HUVECs), and vascularization in chorioallantoic membrane (CAM) assay. Ad-F-UCP increased the vessel density in the Martigel plug assay, and generated copious vessel-like structures in the explanted muscle. The UCP effect on angiogenesis was dependent on VEGF and FGF-2. In mouse hindlimb ischemia model (N = 30/group), autoamputation (limb loss) occurred in 87% and 68% of the mice with saline and Ad encoding Β-galactosidase (Ad-LacZ), respectively, whereas only 23% of the mice injected with Ad-F-UCP showed autoamputation after 21 days of treatment. Ad-F-UCP increased protein levels of HIF-1α, platelet-endothelial cell adhesion molecule-1 (PECAM-1), smooth muscle cell actin (SMA) in the ischemic muscle, and augmented blood vessels doubly positive for PECAM-1 and SMA. Consequently, UCP gene transfer prevented muscle degeneration and autoamputation of ischemic limb. The results suggest that E2-EPF UCP may be a target for therapeutic angiogenesis.-
dc.publisherElsevier-Cell Press-
dc.titleAdenovirus-mediated E2-EPF UCP gene transfer prevents autoamputation in a mouse model of hindlimb ischemia-
dc.title.alternativeAdenovirus-mediated E2-EPF UCP gene transfer prevents autoamputation in a mouse model of hindlimb ischemia-
dc.citation.titleMolecular Therapy-
dc.contributor.affiliatedAuthorJung Hwa Lim-
dc.contributor.affiliatedAuthorHyo-Jung Shin-
dc.contributor.affiliatedAuthorKyeong Su Park-
dc.contributor.affiliatedAuthorCho-Rok Jung-
dc.contributor.affiliatedAuthorDong Soo Im-
dc.identifier.bibliographicCitationMolecular Therapy, vol. 20, no. 4, pp. 778-787-
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Division of Research on National Challenges > Stem Cell Convergenece Research Center > 1. Journal Articles
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