Impaired angiogenesis and mobilization of circulating angiogenic cells in HIF-1alpha heterozygous-null mice after burn wounding.
Impaired angiogenesis and mobilization of circulating angiogenic cells in HIF-1alpha heterozygous-null mice after burn wounding.
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DOI：
10.1111/j.1524-475x.2010.00570.x
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发表时间：
2010-03
期刊：
影响因子：
--
通讯作者：
Semenza GL
中科院分区：
文献类型：
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作者：
Zhang X;Liu L;Wei X;Tan YS;Tong L;Chang R;Ghanamah MS;Reinblatt M;Marti GP;Harmon JW;Semenza GL
缺氧诱导因子 1 (HIF-1) 是一种转录因子，控制血管对缺氧和缺血的反应。在这项研究中，编码 HIF-1α 亚基的基因座上无效等位基因杂合的小鼠（HET 小鼠）及其野生型（WT）同窝小鼠遭受了涉及 10% 体表面积的热损伤。第 2 天，WT 小鼠烧伤创面中的 HIF-1α 蛋白水平升高，而 HET 小鼠则没有。与 CXCR4 结合的基质衍生因子 1α 的血清水平在第 2 天在 WT 中升高，而 HET 小鼠则没有升高。 WT 小鼠中的循环血管生成细胞在第 2 天也有所增加，但 HET 小鼠中没有，并且包括 CXCR4+Sca1+ 细胞。激光多普勒灌注成像显示，第 7 天，WT 小鼠烧伤创面的血流量增加，而 HET 小鼠则没有。第 7 天的免疫组织化学显示，与 WT 小鼠相比，HET 烧伤创面愈合边缘的 CD31+ 血管数量减少。根据第 21 天的 α-平滑肌肌动蛋白阳性血管的数量确定，HET 小鼠伤口中的血管成熟也受到损害。与 WT 同窝小鼠相比，第 14 天的剩余伤口面积在 HET 小鼠中显着增加。 HET 小鼠的第 14 天伤口愈合百分比显着下降。这些数据描绘了 HIF-1 在烧伤伤口愈合过程中促进血管生成的信号传导途径。
Hypoxia-inducible factor 1 (HIF-1) is a transcription factor that controls vascular responses to hypoxia and ischemia. In this study, mice that were heterozygous for a null allele at the locus encoding the HIF-1α subunit (HET mice) and their wild type (WT) littermates were subjected to thermal injury involving 10% of body surface area. HIF-1α protein levels were increased in burn wounds of WT but not of HET mice on day 2. Serum levels of stromal-derived factor 1α, which binds to CXCR4, were increased on day 2 in WT but not in HET mice. Circulating angiogenic cells were also increased on day 2 in WT but not in HET mice and included CXCR4+Sca1+ cells. Laser Doppler perfusion imaging demonstrated increased blood flow in burn wounds of WT but not HET mice on day 7. Immunohistochemistry on day 7 revealed a reduced number of CD31+ vessels at the healing margin of burn wounds in HET as compared to WT mice. Vessel maturation was also impaired in wounds of HET mice as determined by the number of α-smooth muscle actin-positive vessels on day 21. The remaining wound area on day 14 was significantly increased in HET mice compared to WT littermates. The percentage of healed wounds on day 14 was significantly decreased in HET mice. These data delineate a signaling pathway by which HIF-1 promotes angiogenesis during burn wound healing.