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

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.

• Authors: Diana H Yu, Kimberly A Mace, Scott L Hansen, Nancy Boudreau, David M Young
• Journal: Wound repair and regeneration : official publication of the Wound Healing Society [and] the European Tissue Repair Society (Wound Repair Regen) 2007 Sep-Oct Vol. 15 Issue 5 Pg. 628-35 ISSN: 1067-1927 [Print] United States
• PMID: 17971008 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)

Chemical References

• Hif1a protein, mouse
• Hypoxia-Inducible Factor 1, alpha Subunit
• Receptors, Leptin
• Vascular Endothelial Growth Factor A
• leptin receptor, mouse
• vascular endothelial growth factor A, mouse
• Insulin-Like Growth Factor I
• Phosphatidylinositol 3-Kinases
• Ribosomal Protein S6 Kinases, 70-kDa

Topics

• Animals
• Blotting, Western
• Diabetes Mellitus (physiopathology)
• Disease Models, Animal
• Fibroblasts (physiology)
• Hypoxia-Inducible Factor 1, alpha Subunit (biosynthesis, physiology)
• Insulin-Like Growth Factor I (analysis, physiology)
• Mice
• Mice, Inbred Strains
• Phosphatidylinositol 3-Kinases (physiology)
• Receptors, Leptin (deficiency)
• Ribosomal Protein S6 Kinases, 70-kDa (metabolism)
• Skin (chemistry)
• Vascular Endothelial Growth Factor A (physiology)
• Wound Healing (physiology)