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

Stephen A. Watt, Jasbani H.S. Dayal, Sheila Wright, Megan Riddle, Celine Pourreyron, James R. McMillan, Roy M. Kimble, Marco Prisco, Ulrike Gartner, Emma Warbrick, W. H. Irwin McLean, Irene M. Leigh, John A. McGrath, Julio C. Salas-Alanis, Jakub Tolar, Andrew P. South

研究成果: Article同行評審

20 引文 斯高帕斯(Scopus)

摘要

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.

原文English
文章編號e0137639
期刊PloS one
10
發行號9
DOIs
出版狀態Published - 2015 9月 18

All Science Journal Classification (ASJC) codes

  • 多學科

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