Lysyl hydroxylase 3 localizes to epidermal basement membrane and is reduced in patients with recessive dystrophic epidermolysis bullosa

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. (2015) Lysyl hydroxylase 3 localizes to epidermal basement membrane and is reduced in patients with recessive dystrophic epidermolysis bullosa. PLoS One, 10 9: 1-15. doi:10.1371/journal.pone.0137639


Author 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
South, Andrew P.
Title Lysyl hydroxylase 3 localizes to epidermal basement membrane and is reduced in patients with recessive dystrophic epidermolysis bullosa
Journal name PLoS One   Check publisher's open access policy
ISSN 1932-6203
Publication date 2015-09-18
Year available 2015
Sub-type Article (original research)
DOI 10.1371/journal.pone.0137639
Open Access Status DOI
Volume 10
Issue 9
Start page 1
End page 15
Total pages 15
Place of publication San Francisco, CA United States
Publisher Public Library of Science
Language eng
Subject 1300 Biochemistry, Genetics and Molecular Biology
1100 Agricultural and Biological Sciences
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.
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2016 Collection
School of Medicine Publications
 
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