|
  
- 积分
- 0
- 威望
- 0
- 包包
- 3465
|
Gurtner/Macmillan
0 u' B9 A: J6 \7 a' S+ |8 r3 d4 q+ Z' L$ K
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).
. J; X' ~( f$ N5 S
" q8 u" e0 E7 b( T% JStem 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.. P# J* ^. h4 J6 c0 N: r+ i! e
( J j9 s" j$ I4 K& b# a$ |Gurtner'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.) k) E) Q( @" T& Q1 _: Z
+ O8 C- \* H# J6 C* Y; f. R( XProgenitors 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."5 A U1 Z+ \) O# h3 b
7 E2 I9 i& ?& p3 ^2 t- X: x$ I+ g- Q
HIF-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.& @3 _' O i' t) Y. J* A
: g! u3 u* F% F' g/ o- `7 N. P8 }9 RReference:7 e( B$ I1 R2 l% V
# H5 p* t; x& ]; M4 `
Ceradini, D., et al. 2004. Nat. Med. doi:10.1038/nm1075.(SDF1 (red) calls progenitor cells to end) |
|
发表于 2009-3-6 08:16
发表于 2015-6-12 06:55
