Ephrin-A2 affects wound healing and scarring in a murine model of excisional injury

Dulharie Wijeratne; Jennifer Rodger; Andrew Stevenson; Hilary Wallace; Cecilia M Prêle; Fiona M Wood; Mark W Fear

doi:10.1016/j.burns.2018.10.002

Ephrin-A2 affects wound healing and scarring in a murine model of excisional injury

Burns. 2019 May;45(3):682-690. doi: 10.1016/j.burns.2018.10.002. Epub 2018 Oct 25.

Authors

Dulharie Wijeratne¹, Jennifer Rodger², Andrew Stevenson¹, Hilary Wallace¹, Cecilia M Prêle³, Fiona M Wood⁴, Mark W Fear⁵

Affiliations

¹ Burn Injury Research Unit, School of Biomedical Sciences, The University of Western Australia, Australia.
² Experimental and Regenerative Neurosciences, School of Biological Sciences, The University of Western Australia, Australia.
³ The Institute for Respiratory Health, The University of Western Australia, Nedlands, Western Australia, Australia; Centre for Cell Therapy and Regenerative Medicine, School of Biomedical Sciences, The University of Western Australia, Crawley, Western Australia, Australia.
⁴ Burn Injury Research Unit, School of Biomedical Sciences, The University of Western Australia, Australia; Centre for Cell Therapy and Regenerative Medicine, School of Biomedical Sciences, The University of Western Australia, Crawley, Western Australia, Australia; The Fiona Wood Foundation, Perth, Western Australia, Australia; Burns Service of Western Australia, WA Department of Health, Perth, Western Australia, Australia.
⁵ Burn Injury Research Unit, School of Biomedical Sciences, The University of Western Australia, Australia; The Institute for Respiratory Health, The University of Western Australia, Nedlands, Western Australia, Australia; The Fiona Wood Foundation, Perth, Western Australia, Australia. Electronic address: Mark.fear@uwa.edu.au.

PMID: 30482614
DOI: 10.1016/j.burns.2018.10.002

Abstract

Ephrin ligand/Eph receptor signaling is important in both tissue development and homeostasis. There is increasing evidence that Ephrin/Eph signaling is important in the skin, involved in hair follicle cycling, epidermal differentiation, cutaneous innervation and skin cancer. However, there is currently limited information on the role of Ephrin/Eph signaling in cutaneous wound healing. Here we report the effects of the Ephrin-A2 and A5 ligands on wound healing. Using Ephrin-A2^-/-, Ephrin-A5^-/- and Ephrin-A2A5^-/- transgenic mice, in vitro wound healing assays were conducted using isolated keratinocytes and fibroblasts. Ephrin-A2^-/-, Ephrin-A2A5^-/- and wild type mice with excisional wounds were used to analyze the impact of these ligands on wound closure, scar outcome, collagen orientation and re-innervation in vivo. The absence of the Ephrin-A2 and A5 ligands did not have any effect on dermal fibroblast proliferation or on fibroblast or keratinocyte migration. The loss of Ephrin-A2 and A5 ligands did not impact on the rate of wound closure or re-innervation after injury. However, changes in the gross morphology of the healed scar and in collagen histology of the scar dermis were observed in transgenic mice. Therefore Ephrin-A2 and A5 ligands may play an important role in final scar appearance associated with collagen deposition and structure.

Keywords: Collagen; Ephrin A2; Keratinocyte; Scarring; Wound repair.

MeSH terms

Animals
Cell Movement / genetics
Cell Proliferation / genetics
Cicatrix / genetics*
Cicatrix / pathology
Collagen
Ephrin-A2 / genetics*
Ephrin-A5 / genetics*
Fibroblasts
Keratinocytes
Mice
Mice, Knockout
Mice, Transgenic
Surgical Wound / pathology*
Wound Healing / genetics*

Substances

Ephrin-A2
Ephrin-A5
Collagen