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Effects of decreased insulin-like growth factor-1 stimulation on hypoxia inducible factor 1-α protein synthesis and function during cutaneous repair in diabetic mice

Surgical Research Laboratory at San Francisco General Hospital, Department of Surgery, University of California-San Francisco, San Francisco, California 94143-1302, USA.
Wound Repair and Regeneration (Impact Factor: 2.77). 09/2007; 15(5):628-35. DOI: 10.1111/j.1524-475X.2007.00274.x
Source: PubMed

ABSTRACT 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.

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