PMID- 15235597
OWN - NLM
STAT- MEDLINE
DCOM- 20041004
LR  - 20220409
IS  - 1078-8956 (Print)
IS  - 1078-8956 (Linking)
VI  - 10
IP  - 8
DP  - 2004 Aug
TI  - Progenitor cell trafficking is regulated by hypoxic gradients through HIF-1 
      induction of SDF-1.
PG  - 858-64
AB  - 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.
FAU - Ceradini, Daniel J
AU  - Ceradini DJ
AD  - 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.
FAU - Kulkarni, Anita R
AU  - Kulkarni AR
FAU - Callaghan, Matthew J
AU  - Callaghan MJ
FAU - Tepper, Oren M
AU  - Tepper OM
FAU - Bastidas, Nicholas
AU  - Bastidas N
FAU - Kleinman, Mark E
AU  - Kleinman ME
FAU - Capla, Jennifer M
AU  - Capla JM
FAU - Galiano, Robert D
AU  - Galiano RD
FAU - Levine, Jamie P
AU  - Levine JP
FAU - Gurtner, Geoffrey C
AU  - Gurtner GC
LA  - eng
GR  - EB002265/EB/NIBIB NIH HHS/United States
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
DEP - 20040704
PL  - United States
TA  - Nat Med
JT  - Nature medicine
JID - 9502015
RN  - 0 (Chemokine CXCL12)
RN  - 0 (Chemokines, CXC)
RN  - 0 (Cxcl12 protein, mouse)
RN  - 0 (DNA-Binding Proteins)
RN  - 0 (Hif1a protein, mouse)
RN  - 0 (Hypoxia-Inducible Factor 1)
RN  - 0 (Hypoxia-Inducible Factor 1, alpha Subunit)
RN  - 0 (Nuclear Proteins)
RN  - 0 (Receptors, CXCR4)
RN  - 0 (Transcription Factors)
SB  - IM
MH  - Analysis of Variance
MH  - Animals
MH  - Bone Marrow/metabolism
MH  - Cell Adhesion/physiology
MH  - Cell Hypoxia/physiology
MH  - Cell Movement/*physiology
MH  - Chemokine CXCL12
MH  - Chemokines, CXC/*metabolism/physiology
MH  - DNA-Binding Proteins/*metabolism
MH  - Disease Models, Animal
MH  - Endothelial Cells/metabolism
MH  - Enzyme-Linked Immunosorbent Assay
MH  - *Gene Expression Regulation
MH  - Hypoxia-Inducible Factor 1
MH  - Hypoxia-Inducible Factor 1, alpha Subunit
MH  - In Situ Hybridization
MH  - Ischemia/*metabolism
MH  - Mice
MH  - Mice, Nude
MH  - Nuclear Proteins/*metabolism
MH  - Precipitin Tests
MH  - Receptors, CXCR4/metabolism
MH  - Reverse Transcriptase Polymerase Chain Reaction
MH  - Stem Cells/*physiology
MH  - *Transcription Factors
EDAT- 2004/07/06 05:00
MHDA- 2004/10/05 09:00
CRDT- 2004/07/06 05:00
PHST- 2004/04/09 00:00 [received]
PHST- 2004/06/02 00:00 [accepted]
PHST- 2004/07/06 05:00 [pubmed]
PHST- 2004/10/05 09:00 [medline]
PHST- 2004/07/06 05:00 [entrez]
AID - nm1075 [pii]
AID - 10.1038/nm1075 [doi]
PST - ppublish
SO  - Nat Med. 2004 Aug;10(8):858-64. doi: 10.1038/nm1075. Epub 2004 Jul 4.