Progenitor cell trafficking is regulated by hypoxic gradients through HIF-1 induction of SDF-1
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- 4 July 2004
- journal article
- research article
- Published by Springer Science and Business Media LLC in Nature Medicine
- Vol. 10 (8), 858-864
- https://doi.org/10.1038/nm1075
Abstract
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 cells1, 2. SDF-1 and CXCR4 are expressed in complementary patterns during embryonic organogenesis and guide primordial stem cells to sites of rapid vascular expansion3. However, the regulation of SDF-1 and its physiological role in peripheral tissue repair remain incompletely understood4. 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.Keywords
This publication has 30 references indexed in Scilit:
- Targeting HIF-1 for cancer therapyNature Reviews Cancer, 2003
- Effect of stromal-cell-derived factor 1 on stem-cell homing and tissue regeneration in ischaemic cardiomyopathyThe Lancet, 2003
- HGF, SDF-1, and MMP-9 are involved in stress-induced human CD34+ stem cell recruitment to the liverJCI Insight, 2003
- Stromal Cell–Derived Factor-1 Effects on Ex Vivo Expanded Endothelial Progenitor Cell Recruitment for Ischemic NeovascularizationCirculation, 2003
- Human Endothelial Progenitor Cells From Type II Diabetics Exhibit Impaired Proliferation, Adhesion, and Incorporation Into Vascular StructuresCirculation, 2002
- Hypoxia‐induced production of stromal cell–derived factor 1 (CXCL12) and vascular endothelial growth factor by synovial fibroblastsArthritis & Rheumatism, 2002
- The chemokine SDF-1 stimulates integrin-mediated arrest of CD34+ cells on vascular endothelium under shear flowJCI Insight, 1999
- Embryonic Expression and Function of the Chemokine SDF-1 and Its Receptor, CXCR4Developmental Biology, 1999
- Stromal Cell-derived Factor-1α Associates with Heparan Sulfates through the First β-Strand of the ChemokinePublished by Elsevier BV ,1999
- Dependence of Human Stem Cell Engraftment and Repopulation of NOD/SCID Mice on CXCR4Science, 1999