rdf:type |
|
lifeskim:mentions |
umls-concept:C0038250,
umls-concept:C0205263,
umls-concept:C0215848,
umls-concept:C0218504,
umls-concept:C0242184,
umls-concept:C0599896,
umls-concept:C0812409,
umls-concept:C0851285,
umls-concept:C1822686,
umls-concept:C2348110,
umls-concept:C2348977
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pubmed:issue |
8
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pubmed:dateCreated |
2004-8-2
|
pubmed:abstractText |
The trafficking of circulating stem and progenitor cells to areas of tissue damage is poorly understood. The chemokine stromal cell-derived factor-1 (SDF-1 or CXCL12) mediates homing of stem cells to bone marrow by binding to CXCR4 on circulating cells. SDF-1 and CXCR4 are expressed in complementary patterns during embryonic organogenesis and guide primordial stem cells to sites of rapid vascular expansion. However, the regulation of SDF-1 and its physiological role in peripheral tissue repair remain incompletely understood. Here we show that SDF-1 gene expression is regulated by the transcription factor hypoxia-inducible factor-1 (HIF-1) in endothelial cells, resulting in selective in vivo expression of SDF-1 in ischemic tissue in direct proportion to reduced oxygen tension. HIF-1-induced SDF-1 expression increases the adhesion, migration and homing of circulating CXCR4-positive progenitor cells to ischemic tissue. Blockade of SDF-1 in ischemic tissue or CXCR4 on circulating cells prevents progenitor cell recruitment to sites of injury. Discrete regions of hypoxia in the bone marrow compartment also show increased SDF-1 expression and progenitor cell tropism. These data show that the recruitment of CXCR4-positive progenitor cells to regenerating tissues is mediated by hypoxic gradients via HIF-1-induced expression of SDF-1.
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pubmed:grant |
|
pubmed:language |
eng
|
pubmed:journal |
|
pubmed:citationSubset |
IM
|
pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Chemokine CXCL12,
http://linkedlifedata.com/resource/pubmed/chemical/Chemokines, CXC,
http://linkedlifedata.com/resource/pubmed/chemical/Cxcl12 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/DNA-Binding Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Hif1a protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Hypoxia-Inducible Factor 1,
http://linkedlifedata.com/resource/pubmed/chemical/Hypoxia-Inducible Factor 1, alpha...,
http://linkedlifedata.com/resource/pubmed/chemical/Nuclear Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, CXCR4,
http://linkedlifedata.com/resource/pubmed/chemical/Transcription Factors
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pubmed:status |
MEDLINE
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pubmed:month |
Aug
|
pubmed:issn |
1078-8956
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pubmed:author |
|
pubmed:issnType |
Print
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pubmed:volume |
10
|
pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
|
pubmed:pagination |
858-64
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pubmed:dateRevised |
2007-11-15
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pubmed:meshHeading |
pubmed-meshheading:15235597-Analysis of Variance,
pubmed-meshheading:15235597-Animals,
pubmed-meshheading:15235597-Bone Marrow,
pubmed-meshheading:15235597-Cell Adhesion,
pubmed-meshheading:15235597-Cell Hypoxia,
pubmed-meshheading:15235597-Cell Movement,
pubmed-meshheading:15235597-Chemokine CXCL12,
pubmed-meshheading:15235597-Chemokines, CXC,
pubmed-meshheading:15235597-DNA-Binding Proteins,
pubmed-meshheading:15235597-Disease Models, Animal,
pubmed-meshheading:15235597-Endothelial Cells,
pubmed-meshheading:15235597-Enzyme-Linked Immunosorbent Assay,
pubmed-meshheading:15235597-Gene Expression Regulation,
pubmed-meshheading:15235597-Hypoxia-Inducible Factor 1,
pubmed-meshheading:15235597-Hypoxia-Inducible Factor 1, alpha Subunit,
pubmed-meshheading:15235597-In Situ Hybridization,
pubmed-meshheading:15235597-Ischemia,
pubmed-meshheading:15235597-Mice,
pubmed-meshheading:15235597-Mice, Nude,
pubmed-meshheading:15235597-Nuclear Proteins,
pubmed-meshheading:15235597-Precipitin Tests,
pubmed-meshheading:15235597-Receptors, CXCR4,
pubmed-meshheading:15235597-Reverse Transcriptase Polymerase Chain Reaction,
pubmed-meshheading:15235597-Stem Cells,
pubmed-meshheading:15235597-Transcription Factors
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pubmed:year |
2004
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pubmed:articleTitle |
Progenitor cell trafficking is regulated by hypoxic gradients through HIF-1 induction of SDF-1.
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pubmed:affiliation |
Laboratory of Microvascular Research and Vascular Tissue Engineering, Institute of Reconstructive Plastic Surgery, New York University School of Medicine, New York, New York 10016, USA.
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pubmed:publicationType |
Journal Article,
Comparative Study,
Research Support, U.S. Gov't, P.H.S.,
Research Support, Non-U.S. Gov't
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