title: Estrogen receptor-mediated signalling in female mice is locally activated in response to wounding.
abstract: Estrogen deprivation is associated with delayed healing, while Hormone Replacement Therapy (HRT) accelerates acute wound healing and protects against development of chronic wounds. Estrogen exerts its effects on healing via numerous cell types by signalling through the receptors ERα and ERβ, which bind to the Estrogen Responsive Element (ERE) and initiate gene transcription. The ERE-luciferase transgenic mouse model has been influential in assessing real-time in vivo estrogen receptor activation across a range of tissues and pathologies. Using this model we demonstrate novel temporally regulated peri-wound activation of estrogen signalling in female mice. Using histological methods we reveal that this signal is specifically localised to keratinocytes of the neoepidermis and wound margin dermal cells. Moreover using pharmacological agonists we reveal that ERβ induces ERE-mediated signal in both epidermal and dermal cells while ERα induces ERE-mediated signal in dermal cells alone. Collectively these novel data demonstrate rapid and regional activation of estrogen signalling in wounded skin. A more complete understanding of local hormonal signalling during repair is essential for the focussed development of new therapies for wound healing.
authors.affiliation: The Healing Foundation Centre, Faculty of Life Sciences, The University of Manchester, AV Hill Building, Oxford Road, Manchester M13 9PT, UK.
authors.forename: Elaine
authors.initials: E
authors.lastname: Emmerson
authors.forename: Gianpaolo
authors.initials: G
authors.lastname: Rando
authors.forename: Clara
authors.initials: C
authors.lastname: Meda
authors.forename: Laura
authors.initials: L
authors.lastname: Campbell
authors.forename: Adriana
authors.initials: A
authors.lastname: Maggi
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Hardman
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D004958:Estradiol / Q000494:pharmacology / Q000502:physiology; D047628:Estrogen Receptor alpha / Q000378:metabolism*; D047629:Estrogen Receptor beta / Q000378:metabolism*; D004967:Estrogens / Q000494:pharmacology / Q000502:physiology; D005260:Female; D015603:Keratinocytes / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D020218:Response Elements; D015398:Signal Transduction; D012867:Skin / Q000503:physiopathology; D015533:Transcriptional Activation; D014945:Wound Healing
chemical_list: D047628:Estrogen Receptor alpha; D047629:Estrogen Receptor beta; D004967:Estrogens; D004958:Estradiol