Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
8
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.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Aug
pubmed:issn
1078-8956
pubmed:author
pubmed:issnType
Print
pubmed:volume
10
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
858-64
pubmed:dateRevised
2007-11-15
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
pubmed:year
2004
pubmed:articleTitle
Progenitor cell trafficking is regulated by hypoxic gradients through HIF-1 induction of SDF-1.
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.
pubmed:publicationType
Journal Article, Comparative Study, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't