Cooper, F, Overmiller, AM, Loder, A et al. (8 more authors) (2018) Enhancement of cutaneous wound healing by Dsg2 augmentation of uPAR secretion. Journal of Investigative Dermatology, 138 (11). p. 2470. ISSN 0022-202X
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. While low-level Dsg2 expression is observed in basal keratinocytes and is downregulated in non-healing venous ulcers, overexpression has been observed in both melanomas and non-melanoma 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 (uPAR). Dsg2 induced uPAR expression in the skin of transgenic compared to wild-type mice. Wound healing further enhanced uPAR in both epidermis and dermis with concomitant increase in the pro-healing 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 uPAR-related signaling cascades.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | (c) 2018, The Authors. Published by Elsevier, Inc. on behalf of the Society for Investigative Dermatology. This is an author-produced version of a paper published in the Journal of Investigative Dermatology. Uploaded in accordance with the publisher's self-archiving policy. |
Keywords: | Carcinogenesis; Desmoglein 2; Exosomes; Keratinocyte; uPAR; Wound healing. |
Dates: |
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Institution: | The University of Leeds |
Academic Units: | The University of Leeds > Faculty of Medicine and Health (Leeds) > Institute of Molecular Medicine (LIMM) (Leeds) > Section of Experimental Oncology (Leeds) The University of Leeds > Faculty of Medicine and Health (Leeds) > School of Medicine (Leeds) > Leeds Institute of Cancer and Pathology (LICAP) > Section of Experimental Oncology (Leeds) |
Depositing User: | Symplectic Publications |
Date Deposited: | 15 May 2018 14:14 |
Last Modified: | 09 May 2019 00:43 |
Status: | Published |
Publisher: | Elsevier |
Identification Number: | 10.1016/j.jid.2018.04.024 |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:130848 |