Progenitor cell trafficking is regulated by hypoxic gradients through HIF-1 induction of SDF-1

被引：2138

作者：

Ceradini, DJ ^{[1
]}

Kulkarni, AR ^{[1
]}

Callaghan, MJ ^{[1
]}

Tepper, OM ^{[1
]}

Bastidas, N ^{[1
]}

Kleinman, ME ^{[1
]}

Capla, JM ^{[1
]}

Galiano, RD ^{[1
]}

Levine, JP ^{[1
]}

Gurtner, GC ^{[1
]}

机构：

[1] NYU, Sch Med, Inst Reconstruct Plast Surg, Lab Microvasc Res & Vasc Tissue Engn, New York, NY 10016 USA

来源：

NATURE MEDICINE | 2004年 / 10卷 / 08期

关键词：

D O I：

10.1038/nm1075

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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(1,2). SDF-1 and CXCR4 are expressed in complementary patterns during embryonic organogenesis and guide primordial stem cells to sites of rapid vascular expansion(3). However, the regulation of SDF-1 and its physiological role in peripheral tissue repair remain incompletely understood(4). 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.

引用

页码：858 / 864

页数：7

共 30 条

[1] Stromal cell-derived factor-1α associates with heparan sulfates through the first β-strand of the chemokine [J].