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

in Journal of Endocrinology
Authors:
Rita E Roberts Center for Wound Healing and Tissue Regeneration, University of Illinois at Chicago, Chicago, Illinois, USA
Department of Kinesiology and Nutrition, University of Illinois at Chicago, Chicago, Illinois, USA
Research and Development Division, Jesse Brown Veterans Affairs Medical Center, Chicago, Illinois, USA

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Jacqueline Cavalcante-Silva Center for Wound Healing and Tissue Regeneration, University of Illinois at Chicago, Chicago, Illinois, USA
Department of Kinesiology and Nutrition, University of Illinois at Chicago, Chicago, Illinois, USA
Research and Development Division, Jesse Brown Veterans Affairs Medical Center, Chicago, Illinois, USA

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Rhonda D Kineman Research and Development Division, Jesse Brown Veterans Affairs Medical Center, Chicago, Illinois, USA
Section of Endocrinology, Diabetes, and Metabolism, Department of Medicine, University of Illinois at Chicago, Chicago, Illinois, USA

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Timothy J Koh Center for Wound Healing and Tissue Regeneration, University of Illinois at Chicago, Chicago, Illinois, USA
Department of Kinesiology and Nutrition, University of Illinois at Chicago, Chicago, Illinois, USA
Research and Development Division, Jesse Brown Veterans Affairs Medical Center, Chicago, Illinois, USA

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Correspondence should be addressed to T J Koh: tjkoh@uic.edu
DOI:
https://doi.org/10.1530/JOE-21-0298
Volume/Issue:
Volume 252: Issue 1
Article Type:
Research Article
Page Range:
59–70
Online Publication Date:
24 Nov 2021
Copyright:
© Society for Endocrinology 2021
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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.

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Print ISSN:
0022-0795
Online ISSN:
1479-6805
Copyright:
© Society for Endocrinology 2021
Page(s):
12
Article Type:
Research Article
Received Date:
18 Oct 2021
Accepted Date:
27 Oct 2021
Print Publication Date:
01 Jan 2022
Online Publication Date:
24 Nov 2021
Keywords:
IGF; wound healing; skin; mouse

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