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

Authors

  • Diana H. Yu BA,

    1. Surgical Research Laboratory at San Francisco General Hospital, Department of Surgery, University of California-San Francisco, San Francisco, California
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  • Kimberly A. Mace PhD,

    1. Surgical Research Laboratory at San Francisco General Hospital, Department of Surgery, University of California-San Francisco, San Francisco, California
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  • Scott L. Hansen MD,

    1. Surgical Research Laboratory at San Francisco General Hospital, Department of Surgery, University of California-San Francisco, San Francisco, California
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  • Nancy Boudreau PhD,

    1. Surgical Research Laboratory at San Francisco General Hospital, Department of Surgery, University of California-San Francisco, San Francisco, California
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  • David M. Young MD

    1. Surgical Research Laboratory at San Francisco General Hospital, Department of Surgery, University of California-San Francisco, San Francisco, California
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Reprint requests:
David M. Young, MD, Surgical Research Laboratory at San Francisco General Hospital, Department of Surgery, University of California-San Francisco, Box 1302,
San Francisco, CA 94143-1302.
Tel: +415 206 4625;
Fax: +415 206 6997;
Email: dyoung@sfghsurg.ucsf.edu

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-α (Hif-1α) 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-1α protein synthesis and activity in diabetic wounds. We provide evidence that Igf-1 regulates Hif-1α 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-1α protein synthesis and function in vivo.

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