Liver is a primary source of insulin-like growth factor-1 in skin wound healing

in Journal of Endocrinology
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  • 1 Center for Wound Healing and Tissue Regeneration, University of Illinois at Chicago, Chicago, Illinois, USA
  • | 2 Department of Kinesiology and Nutrition, University of Illinois at Chicago, Chicago, Illinois, USA
  • | 3 Research and Development Division, Jesse Brown Veterans Affairs Medical Center, Chicago, Illinois, USA
  • | 4 Section of Endocrinology, Diabetes, and Metabolism, Department of Medicine, University of Illinois at Chicago, Chicago, Illinois, USA

Correspondence should be addressed to T J Koh: tjkoh@uic.edu
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Insulin-like growth factor (IGF)-1 plays important role in tissue repair through its ability to stimulate wound cell activity. While IGF-1 is expressed locally by wound cells, liver-derived IGF-1 is also present at high levels in the circulation, and the contributions of local vs circulating IGF-1 to wound levels remain undefined. The hypothesis of this study was that liver is a primary source of IGF-1 during skin wound healing. To test this hypothesis, we utilized a model that allows inducible ablation of IGF-1 specifically in liver of adult mice. We demonstrate that ablation of liver IGF-1 leads to >85% loss of circulating IGF-1 and ~60% decrease in wound IGF-1 during the proliferative phase of healing in both male and female mice. This reduction of liver-derived IGF-1 did not alter local mRNA expression of Igf1 in wounds. Knockdown of liver IGF-1 significantly delayed wound re-epithelialization and reduced granulation tissue formation and collagen deposition. Knockdown of liver IGF-1 also significantly reduced angiogenesis and resulted in persistent macrophage accumulation. In summary, liver is a primary source of IGF-1 in skin wounds and contributes to many aspects of both epithelial and dermal healing.

Supplementary Materials

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