Document Type
Article
Publication Date
9-18-2015
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.
Recommended Citation
Watt, Stephen A; Dayal, Jasbani H S; Wright, Sheila; Riddle, Megan; Pourreyron, Celine; McMillan, James R; Kimble, Roy M; Prisco, Marco; Gartner, Ulrike; Warbrick, Emma; McLean, W H Irwin; Leigh, Irene M; McGrath, John A; Salas-Alanis, Julio C; Tolar, Jakub; and South, Andrew P, "Lysyl Hydroxylase 3 Localizes to Epidermal Basement Membrane and Is Reduced in Patients with Recessive Dystrophic Epidermolysis Bullosa." (2015). Department of Dermatology and Cutaneous Biology Faculty Papers. Paper 46.
https://jdc.jefferson.edu/dcbfp/46
Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 License.
PubMed ID
26380979
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