Expression of Vascular Endothelial Growth Factor Receptor 1 in Bone Marrow-derived Mesenchymal Cells is Dependent on Hypoxia-inducible Factor 1.
From: Vascular Biology Program, Institute for Cell Engineeringe, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA.
The Journal of biological chemistry
- Publish Date: Jun 2006
- ISSN: 0021-9258
- Volume: 281
- Issue: 22
- Pages: 15554-63
- Medium: Print
- Language: English
- Citation (JAMA): Okuyama Hiroaki, Krishnamachary Balaji, Zhou Yi Fu, et al. Expression of Vascular Endothelial Growth Factor Receptor 1 in Bone Marrow-derived Mesenchymal Cells is Dependent on Hypoxia-inducible Factor 1.. J. Biol. Chem. Jun 2006;281:15554-63
Abstract
Bone marrow-derived cells are recruited to sites of ischemia, where they promote tissue vascularization. This response is dependent upon the expression of vascular endothelial growth factor (VEGF) receptor 1 (VEGFR1), which mediates cell migration in response to VEGF or placental growth factor (PLGF). In this study, we found that exposure of cultured mouse bone marrow-derived mesenchymal stromal cells (MSC) to hypoxia or an adenovirus encoding a constitutively active form of hypoxia-inducible factor 1 (HIF-1) induced VEGFR1 mRNA and protein expression and promoted ex vivo migration in response to VEGF or PLGF. MSC in which HIF-1 activity was inhibited by a dominant negative or RNA interference approach expressed markedly reduced levels of VEGFR1 and failed to migrate or activate AKT in response to VEGF or PLGF. Thus, loss-of-function and gain-of-function approaches demonstrated that HIF-1 activity is necessary and sufficient for basal and hypoxia-induced VEGFR1 expression in bone marrow-derived MSC.
Mesh Headings (Keywords): Animals, Bone Marrow Cells, Cell Hypoxia, Cell Movement, Cells, Cultured, Gene Expression, Humans, Hypoxia-Inducible Factor 1, Hypoxia-Inducible Factor 1, alpha Subunit, Mesenchymal Stem Cells, Mice, Mice, Inbred C57BL, Mice, Knockout, RNA Interference, RNA, Messenger, Transfection, Vascular Endothelial Growth Factor Receptor-1
Check for Full Text / PubMed Unique Identifier (PMID): 16574650
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