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HIF1A overexpression using cell-penetrating DNA-binding protein induces angiogenesis in vitro and in vivo

Authors
 Mijeong Jeon  ;  Yooseok Shin  ;  Jaeeun Jung  ;  Ui-Won Jung  ;  Jae-Hoon Lee  ;  Jae-Seung Moon  ;  Ilkoo Kim  ;  Jin-Su Shin  ;  Sang-Kyou Lee  ;  Je Seon Song 
Citation
 Molecular and Cellular Biochemistry, Vol.437(1-2) : 99-107, 2018 
Journal Title
 Molecular and Cellular Biochemistry 
ISSN
 0300-8177 
Issue Date
2018
MeSH
Cell-Penetrating Peptides/*pharmacology ; Human Umbilical Vein Endothelial Cells/cytology/*metabolism ; Humans ; alpha Subunit/*biosynthesis Hypoxia-Inducible Factor 1 ; Physiologic/*drug effects Neovascularization ; Platelet Endothelial Cell Adhesion Molecule-1/biosynthesis ; Vascular Endothelial Growth Factor A/biosynthesis
Keywords
Angiogenesis ; HUVEC ; Hypoxia-inducible factor-1 alpha (HIF1A) ; Protein transduction domain (PTD) ; Tissue regeneration
Abstract
Hypoxia-inducible factor-1 alpha (HIF1A) is an important transcription factor for angiogenesis. Recent studies have used the protein transduction domain (PTD) to deliver genes, but the PTD has not been used to induce the expression of HIF1A. This study aimed at using a novel PTD (Hph-1-GAL4; ARVRRRGPRR) to overexpress the HIF1A and identify the effects on angiogenesis in vitro and in vivo. Overexpression of HIF1A was induced using Hph-1-GAL4 in human umbilical vein/vascular endothelium cells (HUVEC). The expression levels of genes were analyzed by the quantitative real-time polymerase chain reaction (qPCR) after 2 and 4 days, respectively. An in vitro tube formation was performed using Diff-Quik staining. HIF1A and Hph-1-GAL4 were injected subcutaneously into the ventral area of each 5-week-old mouse. All of the plugs were retrieved after 1 week, and the gene expression levels were evaluated by qPCR. Each Matrigel plug was evaluated using the hemoglobin assay and hematoxylin and eosin (HE) staining. The expression levels of HIF1A and HIF1A target genes were significantly higher in HIF1A-transfected HUVEC than in control HUVEC in vitro. In the in vivo Matrigel plug assay, the amount of hemoglobin was significantly higher in the HIF1A-treatment group than in the PBS-treatment group. Blood vessels were identified in the HIF1A-treatment group. The expression levels of HIF1A, vascular endothelial growth factor (Vegf), and Cd31 were significantly higher in the HIF1A-treatment group than in the PBS-treatment group. These findings suggest that using Hph-1-G4D to overexpress HIF1A might be useful for transferring genes and regenerating tissues.
Full Text
https://link.springer.com/article/10.1007%2Fs11010-017-3098-6
DOI
10.1007/s11010-017-3098-6
Appears in Collections:
2. College of Dentistry (치과대학) > Dept. of Conservative Dentistry (보존과학교실) > 1. Journal Papers
2. College of Dentistry (치과대학) > Dept. of Pediatric Dentistry (소아치과학교실) > 1. Journal Papers
2. College of Dentistry (치과대학) > Dept. of Prosthodontics (보철과학교실) > 1. Journal Papers
2. College of Dentistry (치과대학) > Dept. of Periodontics (치주과학교실) > 1. Journal Papers
Yonsei Authors
송제선(Song, Je Seon) ORCID logo https://orcid.org/0000-0001-8620-5629
신유석(Shin, Yoo Seok) ORCID logo https://orcid.org/0000-0003-1121-2570
이재훈(Lee, Jae Hoon) ORCID logo https://orcid.org/0000-0003-2281-8885
정의원(Jung, Ui Won) ORCID logo https://orcid.org/0000-0001-6371-4172
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URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/161871
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