Yu Diana H, Mace Kimberly A, Hansen Scott L, Boudreau Nancy, Young David M
Surgical Research Laboratory at San Francisco General Hospital, Department of Surgery, University of California-San Francisco, San Francisco, California 94143-1302, USA.
Wound Repair Regen. 2007 Sep-Oct;15(5):628-35. doi: 10.1111/j.1524-475X.2007.00274.x.
Insulin-like growth factor-1 (Igf-1), a critical mediator of tissue repair, is significantly decreased in diabetic wounds. Furthermore, decreased levels of hypoxia-inducible factor 1-alpha (Hif-1alpha) and its target genes are also associated with impaired wound healing in diabetic mice. The aim of our study was to examine whether the reduced levels of Igf-1 are responsible for the reduction in Hif-1alpha protein synthesis and activity in diabetic wounds. We provide evidence that Igf-1 regulates Hif-1alpha protein synthesis and activity during wound repair. In addition, Igf-1 stimulated phosphytidylinositol 3-kinase activity in diabetic fibroblasts, which, in turn, increased activation of the translational regulatory protein, p70 S6 kinase. Moreover, improved healing of diabetic wounds by addition of recombinant IGF-1 protein was associated with an increase in Hif-1alpha protein synthesis and function in vivo.
胰岛素样生长因子-1（Igf-1）是组织修复的关键介质，在糖尿病伤口中显著减少。此外，缺氧诱导因子1-α（Hif-1α）及其靶基因水平的降低也与糖尿病小鼠伤口愈合受损有关。我们研究的目的是检查Igf-1水平降低是否是糖尿病伤口中Hif-1α蛋白合成和活性降低的原因。我们提供的证据表明，Igf-1在伤口修复过程中调节Hif-1α蛋白的合成和活性。此外，Igf-1刺激糖尿病成纤维细胞中的磷脂酰肌醇3-激酶活性，进而增加翻译调节蛋白p70 S6激酶的激活。此外，添加重组IGF-1蛋白改善糖尿病伤口愈合与体内Hif-1α蛋白合成和功能增加有关。
