Insulin-like growth factor-1 promotes wound healing in estrogen-deprived mice: new insights into cutaneous IGF-1R/ERα cross talk.
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.
The Healing Foundation Centre, The University of Manchester, Manchester, UK.
Elaine
E
Emmerson
Laura
L
Campbell
Faith C J
FC
Davies
Nina L
NL
Ross
Gillian S
GS
Ashcroft
Andrée
A
Krust
Pierre
P
Chambon
Matthew J
MJ
Hardman
D000818:Animals; D002478:Cells, Cultured; D003872:Dermatitis / Q000188:drug therapy / Q000378:metabolism*; D020405:Dermis / Q000166:cytology / Q000276:immunology; D004195:Disease Models, Animal; D047628:Estrogen Receptor alpha / Q000235:genetics / Q000378:metabolism*; D004967:Estrogens / Q000172:deficiency; D005260:Female; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000378:metabolism* / Q000494:pharmacology; D015603:Keratinocytes / Q000166:cytology / Q000378:metabolism; D017737:Macrophages, Peritoneal / Q000166:cytology / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D010052:Ovariectomy; D020239:Receptor Cross-Talk / Q000187:drug effects / Q000502:physiology; D017526:Receptor, IGF Type 1 / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects / Q000276:immunology*; D014945:Wound Healing / Q000187:drug effects / Q000276:immunology*
D047628:Estrogen Receptor alpha; D004967:Estrogens; D007334:Insulin-Like Growth Factor I; D017526:Receptor, IGF Type 1