TY - JOUR
T1 - 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
AU - Yu, Diana H.
AU - MacE, Kimberly A.
AU - Hansen, Scott L.
AU - Boudreau, Nancy
AU - Young, David M.
PY - 2007/9
Y1 - 2007/9
N2 - 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.
AB - 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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U2 - 10.1111/j.1524-475X.2007.00274.x
DO - 10.1111/j.1524-475X.2007.00274.x
M3 - Article
C2 - 17971008
AN - SCOPUS:34848823534
SN - 1067-1927
VL - 15
SP - 628
EP - 635
JO - Wound Repair and Regeneration
JF - Wound Repair and Regeneration
IS - 5
ER -