Insulin-like growth factor-1 promotes wound healing in estrogen-deprived mice: new insights into cutaneous IGF-1R/ERα cross talk

Elaine Emmerson, Laura Campbell, Faith C J Davies, Nina L Ross, Gillian S Ashcroft, Andrée Krust, Pierre Chambon, Matthew J Hardman

Research output: Contribution to journalArticlepeer-review

Abstract

Although it is understood that endogenous IGF-1 is involved in the wound repair process, the effects of exogenous IGF-1 administration on wound repair remain largely unclear. In addition, the signaling links between IGF-1 receptor (IGF-1R) and estrogen receptors (ERs), which have been elucidated in other systems, have yet to be explored in the context of skin repair. In this study, we show that locally administered IGF-1 promotes wound repair in an estrogen-deprived animal model, the ovariectomized (Ovx) mouse, principally by dampening the local inflammatory response and promoting re-epithelialization. Using specific IGF-1R and ER antagonists in vivo, we reveal that IGF-1-mediated effects on re-epithelialization are directly mediated by IGF-1R. By contrast, the anti-inflammatory effects of IGF-1 are predominantly via the ERs, in particular ERα. Crucially, in ERα-null mice, IGF-1 fails to promote healing, and local inflammation is increased. Our findings illustrate the complex interactions between IGF-1 and estrogen in skin. The fact that IGF-1 may compensate for estrogen deficiency in wound repair, and potentially other contexts, is an important consideration for the treatment of postmenopausal pathology.

Original languageEnglish
Pages (from-to)2838-48
Number of pages11
JournalJournal of Investigative Dermatology
Volume132
Issue number12
DOIs
Publication statusPublished - Dec 2012

Keywords

  • Animals
  • Cells, Cultured
  • Dermatitis
  • Dermis
  • Disease Models, Animal
  • Estrogen Receptor alpha
  • Estrogens
  • Female
  • Fibroblasts
  • Humans
  • Insulin-Like Growth Factor I
  • Keratinocytes
  • Macrophages, Peritoneal
  • Mice
  • Mice, Inbred C57BL
  • Mice, Mutant Strains
  • Ovariectomy
  • Receptor Cross-Talk
  • Receptor, IGF Type 1
  • Signal Transduction
  • Wound Healing
  • Journal Article
  • Research Support, Non-U.S. Gov't

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