Authors

Stephen A Watt, Division of Cancer Research, University of Dundee
Jasbani H S Dayal, Division of Cancer Research, University of Dundee
Sheila Wright, Division of Cancer Research, University of Dundee
Megan Riddle, Stem Cell Institute and Pediatric Blood and Marrow Transplantation, University of Minnesota
Celine Pourreyron, Division of Cancer Research, University of Dundee
James R McMillan, Centre for Children's Burns Research, Queensland Children's Medical Research Institute, Royal Children's Hospital, University of Queensland
Roy M Kimble, Centre for Children's Burns Research, Queensland Children's Medical Research Institute, Royal Children's Hospital, University of Queensland
Marco Prisco, Department of Dermatology and Cutaneous Biology, Thomas Jefferson UniversityFollow
Ulrike Gartner, Centre for Dermatology and Genetic Medicine, Division of Molecular Medicine, Colleges of Life Sciences and Medicine, Dentistry and Nursing, University of Dundee
Emma Warbrick, Centre for Dermatology and Genetic Medicine, Division of Molecular Medicine, Colleges of Life Sciences and Medicine, Dentistry and Nursing, University of Dundee
W H Irwin McLean, Centre for Dermatology and Genetic Medicine, Division of Molecular Medicine, Colleges of Life Sciences and Medicine, Dentistry and Nursing, University of Dundee
Irene M Leigh, Division of Cancer Research, University of Dundee
John A McGrath, St. John's Institute of Dermatology, King's College London (Guy's Campus)
Julio C Salas-Alanis, Basic Sciences Department, Medicine School, University of Monterrey
Jakub Tolar, Stem Cell Institute and Pediatric Blood and Marrow Transplantation, University of Minnesota
Andrew P South, Division of Cancer Research, University of Dundee; Department of Dermatology and Cutaneous Biology, Thomas Jefferson University

Document Type

Article

Publication Date

9-18-2015

Comments

This article has been peer reviewed. It was published in: PLoS ONE.

Volume 10, Issue 9, 18 September 2015, Article number e0137639.

The published version is available at DOI: 10.1371/journal.pone.0137639

Copyright © 2015 Watt et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited

Abstract

Recessive dystrophic epidermolysis bullosa (RDEB) is caused by mutations in COL7A1 resulting in reduced or absent type VII collagen, aberrant anchoring fibril formation and subsequent dermal-epidermal fragility. Here, we identify a significant decrease in PLOD3 expression and its encoded protein, the collagen modifying enzyme lysyl hydroxylase 3 (LH3), in RDEB. We show abundant LH3 localising to the basement membrane in normal skin which is severely depleted in RDEB patient skin. We demonstrate expression is in-part regulated by endogenous type VII collagen and that, in agreement with previous studies, even small reductions in LH3 expression lead to significantly less secreted LH3 protein. Exogenous type VII collagen did not alter LH3 expression in cultured RDEB keratinocytes and we show that RDEB patients receiving bone marrow transplantation who demonstrate significant increase in type VII collagen do not show increased levels of LH3 at the basement membrane. Our data report a direct link between LH3 and endogenous type VII collagen expression concluding that reduction of LH3 at the basement membrane in patients with RDEB will likely have significant implications for disease progression and therapeutic intervention.

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This work is licensed under a Creative Commons Attribution 4.0 License.

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