title: Ectodysplasin A Pathway Contributes to Human and Murine Skin Repair.
abstract: The highly conserved ectodysplasin A (EDA)/EDA receptor signaling pathway is critical during development for the formation of skin appendages. Mutations in genes encoding components of the EDA pathway disrupt normal appendage development, leading to the human disorder hypohidrotic ectodermal dysplasia. Spontaneous mutations in the murine Eda (Tabby) phenocopy human X-linked hypohidrotic ectodermal dysplasia. Little is known about the role of EDA signaling in adult skin homeostasis or repair. Because wound healing largely mimics the morphogenic events that occur during development, we propose a role for EDA signaling in adult wound repair. Here we report a pronounced delay in healing in Tabby mice, demonstrating a functional role for EDA signaling in adult skin. Moreover, pharmacological activation of the EDA pathway in both Tabby and wild-type mice significantly accelerates healing, influencing multiple processes including re-epithelialization and granulation tissue matrix deposition. Finally, we show that the healing promoting effects of EDA receptor activation are conserved in human skin repair. Thus, targeted manipulation of the EDA/EDA receptor pathway has clear therapeutic potential for the future treatment of human pathological wound healing.
authors.affiliation: The Healing Foundation Centre, Faculty of Life Sciences, University of Manchester, Manchester, United Kingdom.
authors.forename: Clare L
authors.initials: CL
authors.lastname: Garcin
authors.affiliation: Edimer Pharmaceuticals Inc, Cambridge, Massachusetts, USA.
authors.forename: Kenneth M
authors.initials: KM
authors.lastname: Huttner
authors.affiliation: Edimer Pharmaceuticals Inc, Cambridge, Massachusetts, USA.
authors.forename: Neil
authors.initials: N
authors.lastname: Kirby
authors.affiliation: Department of Biochemistry, University of Lausanne, Lausanne, Switzerland.
authors.forename: Pascal
authors.initials: P
authors.lastname: Schneider
authors.affiliation: The Healing Foundation Centre, Faculty of Life Sciences, University of Manchester, Manchester, United Kingdom. Electronic address: Matthew.j.hardman@manchester.ac.uk.
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Hardman
mesh_terms: D000818:Animals; D001707:Biopsy, Needle; D004195:Disease Models, Animal; D004476:Ectodermal Dysplasia / Q000235:genetics* / Q000628:therapy; D053331:Ectodysplasins / Q000235:genetics; D053339:Edar Receptor / Q000235:genetics*; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D011897:Random Allocation; D012680:Sensitivity and Specificity; D015398:Signal Transduction / Q000235:genetics*; D014945:Wound Healing / Q000235:genetics* / Q000502:physiology; D014947:Wounds and Injuries / Q000235:genetics* / Q000503:physiopathology
chemical_list: C506008:EDAR protein, human; D053331:Ectodysplasins; D053339:Edar Receptor; C506009:Edar protein, mouse
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