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

Diana H. Yu, Kimberly A. MacE, Scott L. Hansen, Nancy Boudreau, David M. Young

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish (US)
Pages (from-to)628-635
Number of pages8
JournalWound Repair and Regeneration
Volume15
Issue number5
DOIs
StatePublished - Sep 2007

ASJC Scopus subject areas

  • Surgery
  • Dermatology

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