Enhancement of Cutaneous Wound Healing by Dsg2 Augmentation of uPAR Secretion.

Autor:	Cooper F; Department of Dermatology and Cutaneous Biology, Thomas Jefferson University, Philadelphia, Pennsylvania, USA., Overmiller AM; Department of Dermatology and Cutaneous Biology, Thomas Jefferson University, Philadelphia, Pennsylvania, USA., Loder A; Department of Dermatology and Cutaneous Biology, Thomas Jefferson University, Philadelphia, Pennsylvania, USA., Brennan-Crispi DM; Department of Dermatology and Cutaneous Biology, Thomas Jefferson University, Philadelphia, Pennsylvania, USA., McGuinn KP; Department of Dermatology and Cutaneous Biology, Thomas Jefferson University, Philadelphia, Pennsylvania, USA., Marous MR; Department of Dermatology and Cutaneous Biology, Thomas Jefferson University, Philadelphia, Pennsylvania, USA., Freeman TA; Department of Dermatology and Cutaneous Biology, Thomas Jefferson University, Philadelphia, Pennsylvania, USA; Department of Orthopedic Surgery, Thomas Jefferson University, Philadelphia, Pennsylvania, USA., Riobo-Del Galdo NA; Leeds Institute of Cancer and Pathology, University of Leeds, UK., Siracusa LD; Department of Microbiology and Immunology, Thomas Jefferson University, Philadelphia, Pennsylvania, USA., Wahl JK 3rd; Department of Oral Biology, University of Nebraska Medical Center, Lincoln, Nebraska, USA., Mahoney MG; Department of Dermatology and Cutaneous Biology, Thomas Jefferson University, Philadelphia, Pennsylvania, USA. Electronic address: my.mahoney@jefferson.edu.
Jazyk:	angličtina
Zdroj:	The Journal of investigative dermatology [J Invest Dermatol] 2018 Nov; Vol. 138 (11), pp. 2470-2479. Date of Electronic Publication: 2018 May 09.
DOI:	10.1016/j.jid.2018.04.024
Abstrakt:	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. (Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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