Deficiency of liver-derived insulin-like growth factor-I (IGF-I) does not interfere with the skin wound healing rate

PLoS One. 2018 Mar 13;13(3):e0193084. doi: 10.1371/journal.pone.0193084. eCollection 2018.

Abstract

Objective: IGF-I is a growth factor, which is expressed in virtually all tissues. The circulating IGF-I is however derived mainly from the liver. IGF-I promotes wound healing and its levels are decreased in wounds with low regenerative potential such as diabetic wounds. However, the contribution of circulating IGF-I to wound healing is unknown. Here we investigated the role of systemic IGF-I on wound healing rate in mice with deficiency of liver-derived IGF-I (LI-IGF-I-/- mice) during normal (normoglycemic) and impaired wound healing (diabetes).

Methods: LI-IGF-I-/- mice with complete inactivation of the IGF-I gene in the hepatocytes were generated using the Cre/loxP recombination system. This resulted in a 75% reduction of circulating IGF-I. Diabetes was induced with streptozocin in both LI-IGF-I-/- and control mice. Wounds were made on the dorsum of the mice, and the wound healing rate and histology were evaluated. Serum IGF-I and GH were measured by RIA and ELISA respectively. The expression of IGF-I, IGF-II and the IGF-I receptor in the skin were evaluated by qRT-PCR. The local IGF-I protein expression in different cell types of the wounds during wound healing process was analyzed using immunohistochemistry.

Results: The wound healing rate was similar in LI-IGF-I-/- mice to that in controls. Diabetes significantly delayed the wound healing rate in both LI-IGF-I-/- and control mice. However, no significant difference was observed between diabetic animals with normal or reduced hepatic IGF-I production. The gene expression of IGF-I, IGF-II and IGF-I receptor in skin was not different between any group of animals tested. Local IGF-I levels in the wounds were similar between of LI-IGF-I-/- and WT mice although a transient reduction of IGF-I expression in leukocytes in the wounds of LI-IGF-I-/- was observed seven days post wounding.

Conclusion: Deficiency in the liver-derived IGF-I does not affect wound healing in mice, neither in normoglycemic conditions nor in diabetes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Diabetes Complications* / genetics
  • Diabetes Complications* / metabolism
  • Diabetes Complications* / pathology
  • Diabetes Mellitus, Experimental* / genetics
  • Diabetes Mellitus, Experimental* / metabolism
  • Diabetes Mellitus, Experimental* / pathology
  • Hepatocytes* / metabolism
  • Hepatocytes* / pathology
  • Insulin-Like Growth Factor I / deficiency*
  • Insulin-Like Growth Factor I / metabolism
  • Liver / metabolism*
  • Liver / pathology
  • Mice
  • Mice, Knockout
  • Organ Specificity
  • Skin* / injuries
  • Skin* / metabolism
  • Skin* / pathology
  • Wound Healing*

Substances

  • insulin-like growth factor-1, mouse
  • Insulin-Like Growth Factor I

Grants and funding

This work was partly supported by grants from the Swedish Research Council, Family Erling- Persson Foundation, Stockholm County Research Council, ALF Foundation, Bert von Kantzows Foundation, Strategic Research Programme in Diabetes. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.