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Progenitor cell trafficking is regulated by hypoxic gradients through HIF-1 induction of SDF-1.
Nat Med. 2004 Aug; 10(8):858-64.NMed

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 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.

Authors+Show Affiliations

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.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Comparative Study
Journal Article
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

15235597

Citation

Ceradini, Daniel J., et al. "Progenitor Cell Trafficking Is Regulated By Hypoxic Gradients Through HIF-1 Induction of SDF-1." Nature Medicine, vol. 10, no. 8, 2004, pp. 858-64.
Ceradini DJ, Kulkarni AR, Callaghan MJ, et al. Progenitor cell trafficking is regulated by hypoxic gradients through HIF-1 induction of SDF-1. Nat Med. 2004;10(8):858-64.
Ceradini, D. J., Kulkarni, A. R., Callaghan, M. J., Tepper, O. M., Bastidas, N., Kleinman, M. E., Capla, J. M., Galiano, R. D., Levine, J. P., & Gurtner, G. C. (2004). Progenitor cell trafficking is regulated by hypoxic gradients through HIF-1 induction of SDF-1. Nature Medicine, 10(8), 858-64.
Ceradini DJ, et al. Progenitor Cell Trafficking Is Regulated By Hypoxic Gradients Through HIF-1 Induction of SDF-1. Nat Med. 2004;10(8):858-64. PubMed PMID: 15235597.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Progenitor cell trafficking is regulated by hypoxic gradients through HIF-1 induction of SDF-1. AU - Ceradini,Daniel J, AU - Kulkarni,Anita R, AU - Callaghan,Matthew J, AU - Tepper,Oren M, AU - Bastidas,Nicholas, AU - Kleinman,Mark E, AU - Capla,Jennifer M, AU - Galiano,Robert D, AU - Levine,Jamie P, AU - Gurtner,Geoffrey C, Y1 - 2004/07/04/ PY - 2004/04/09/received PY - 2004/06/02/accepted PY - 2004/7/6/pubmed PY - 2004/10/5/medline PY - 2004/7/6/entrez SP - 858 EP - 64 JF - Nature medicine JO - Nat Med VL - 10 IS - 8 N2 - 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. SN - 1078-8956 UR - https://www.unboundmedicine.com/medline/citation/15235597/Progenitor_cell_trafficking_is_regulated_by_hypoxic_gradients_through_HIF_1_induction_of_SDF_1_ L2 - https://doi.org/10.1038/nm1075 DB - PRIME DP - Unbound Medicine ER -