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Cells gasping for air call out to progenitor cells for help, according to results from Daniel Ceradini, Geoffrey Gurtner, and colleagues (NYU School of Medicine, New York, NY).
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Stem cells and progenitor cells do not start making new tissue just anywhere—most often, they are recruited to injury sites. The chemokine SDF-1 is known to trigger this recruitment, but what causes injured tissues to make SDF-1 was unclear.9 Z+ q- q9 k- r2 {. ^4 p2 z# M, Q
; K/ d0 V k! ^4 ~& K: T. q& S+ ^7 UGurtner's group shows that SDF-1 expression is activated by HIF-1, a transcription factor known to be stabilized at low oxygen levels. Tissues with low oxygen and high SDF-1—either injury sites or bone marrow, where progenitors normally hang out—were hot spots for endothelial progenitor cells (EPCs) carrying the SDF-1 receptor, CXCR4. These EPCs adhered better to endothelial cells expressing SDF-1, and they also migrated toward SDF-1 gradients in vitro. Disruption of SDF-1 interactions with CXCR4 prevented EPC homing and blocked vascular regeneration in mice.
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Progenitors for other cell types (neurons, muscle, etc) might also respond to SDF-1, but Gurtner focused on EPCs because new vasculature can both repair and prevent injury. "Endothelial cells downstream of a blood vessel blockage become hypoxic and make SDF-1," he says. "This marks them like a barcode that says this is an area of injury. Often, nothing cataclysmic happens because new vessels form natural bypasses around the blockage."/ Y2 A" a( Y# a- g j( {0 ?
6 Y4 D. X# ~& f8 u; w3 gHIF-1 was already known to induce sprouting of existing blood vessels through the induction of the growth factor VEGF. But hypoxia and HIF-1 were not known to recruit circulating progenitors.
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8 k+ q) I9 x; P. {, g& S8 PCeradini, D., et al. 2004. Nat. Med. doi:10.1038/nm1075.(SDF1 (red) calls progenitor cells to end) |
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发表于 2009-3-6 08:16
发表于 2015-6-12 06:55
