Enhancement of Cutaneous Wound Healing by Dsg2 Augmentation of uPAR Secretion

Felicia Cooper, Andrew M. Overmiller, Anthony Loder, Donna M. Brennan-Crispi, Kathleen P. McGuinn, Molly R. Marous, Theresa A. Freeman, Natalia A. Riobo-Del Galdo, Linda D. Siracusa, James K Wahl, Mỹ G. Mahoney

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2 Scopus citations

Abstract

In addition to playing a role in adhesion, desmoglein 2 (Dsg2) is an important regulator of growth and survival signaling pathways, cell proliferation, migration and invasion, and oncogenesis. Although low-level Dsg2 expression is observed in basal keratinocytes and is downregulated in nonhealing venous ulcers, overexpression has been observed in both melanomas and nonmelanoma malignancies. Here, we show that transgenic mice overexpressing Dsg2 in basal keratinocytes primed the activation of mitogenic pathways, but did not induce dramatic epidermal changes or susceptibility to chemical-induced tumor development. Interestingly, acceleration of full-thickness wound closure and increased wound-adjacent keratinocyte proliferation was observed in these mice. As epidermal cytokines and their receptors play critical roles in wound healing, Dsg2-induced secretome alterations were assessed with an antibody profiler array and revealed increased release and proteolytic processing of the urokinase-type plasminogen activator receptor. Dsg2 induced urokinase-type plasminogen activator receptor expression in the skin of transgenic compared with wild-type mice. Wounding further enhanced urokinase-type plasminogen activator receptor in both epidermis and dermis with a concomitant increase in the prohealing laminin-332, a major component of the basement membrane zone, in transgenic mice. This study demonstrates that Dsg2 induces epidermal activation of various signaling cascades and accelerates cutaneous wound healing, in part, through urokinase-type plasminogen activator receptor-related signaling cascades.

Original languageEnglish (US)
Pages (from-to)2470-2479
Number of pages10
JournalJournal of Investigative Dermatology
Volume138
Issue number11
DOIs
Publication statusPublished - Nov 2018

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ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Dermatology
  • Cell Biology

Cite this

Cooper, F., Overmiller, A. M., Loder, A., Brennan-Crispi, D. M., McGuinn, K. P., Marous, M. R., ... Mahoney, M. G. (2018). Enhancement of Cutaneous Wound Healing by Dsg2 Augmentation of uPAR Secretion. Journal of Investigative Dermatology, 138(11), 2470-2479. https://doi.org/10.1016/j.jid.2018.04.024