Estrogen receptor-mediated signalling in female mice is locally activated in response to wounding

Elaine Emmerson, Gianpaolo Rando, Clara Meda, Laura Campbell, Adriana Maggi, Matthew J Hardman

Research output: Contribution to journalArticlepeer-review

Abstract / Description of output

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.

Original languageEnglish
Pages (from-to)149-56
Number of pages8
JournalMolecular and Cellular Endocrinology
Volume375
Issue number1-2
DOIs
Publication statusPublished - 15 Aug 2013

Keywords / Materials (for Non-textual outputs)

  • Animals
  • Cells, Cultured
  • Estradiol
  • Estrogen Receptor alpha
  • Estrogen Receptor beta
  • Estrogens
  • Female
  • Keratinocytes
  • Mice
  • Mice, Transgenic
  • Response Elements
  • Signal Transduction
  • Skin
  • Transcriptional Activation
  • Wound Healing
  • Journal Article
  • Research Support, Non-U.S. Gov't

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