Ectodysplasin A Pathway Contributes to Human and Murine Skin Repair

Garcin, Clare L.; Huttner, Kenneth M.; Kirby, Neil; Schneider, Pascal; Hardman, Matthew J.

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.

Citation

Garcin, C. L., Huttner, K. M., Kirby, N., Schneider, P., & Hardman, M. J. (2016). Ectodysplasin A Pathway Contributes to Human and Murine Skin Repair. Journal of Investigative Dermatology, 136(5), 1022-1030. https://doi.org/10.1016/j.jid.2015.09.002

• Journal Article Type: Article
• Acceptance Date: Sep 22, 2015
• Online Publication Date: Jan 29, 2016
• Publication Date: 2016-05
• Deposit Date: Feb 4, 2021
• Publicly Available Date: Feb 4, 2021
• Journal: Journal of Investigative Dermatology
• Print ISSN: 0022-202x
• Electronic ISSN: 1523-1747
• Publisher: Elsevier
• Peer Reviewed: Peer Reviewed
• Volume: 136
• Issue: 5
• Pages: 1022-1030
• DOI: https://doi.org/10.1016/j.jid.2015.09.002
• Public URL: https://hull-repository.worktribe.com/output/3587361
• Publisher URL: https://www.jidonline.org/article/S0022-202X(16)00370-5/fulltext