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

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

© 2015 Watt et al. 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.
Original languageEnglish
Article numbere0137639
JournalPLoS One
Volume10
Issue number9
DOIs
Publication statusPublished - 18 Sep 2015

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2-Oxoglutarate 5-Dioxygenase Procollagen-Lysine
epidermolysis bullosa
Epidermolysis Bullosa Dystrophica
basement membrane
Basement Membrane
Collagen Type VII
collagen
Skin
bone marrow transplant
keratinocytes
disease course
proteins
Bone Marrow Transplantation
Keratinocytes
mutation
Disease Progression
therapeutics
Bone
Proteins
Collagen

All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

Cite this

Watt, S. A., Dayal, J. H. S., Wright, S., Riddle, M., Pourreyron, C., McMillan, J. R., ... South, A. P. (2015). Lysyl hydroxylase 3 localizes to epidermal basement membrane and is reduced in patients with recessive dystrophic epidermolysis bullosa. PLoS One, 10(9), [e0137639]. https://doi.org/10.1371/journal.pone.0137639
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 ; Irwin McLean, W. H. ; Leigh, Irene M. ; McGrath, John A. ; Salas-Alanis, Julio C. ; Tolar, Jakub ; South, Andrew P. / Lysyl hydroxylase 3 localizes to epidermal basement membrane and is reduced in patients with recessive dystrophic epidermolysis bullosa. In: PLoS One. 2015 ; Vol. 10, No. 9.
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abstract = "{\circledC} 2015 Watt et al. 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.",
author = "Watt, {Stephen A.} and Dayal, {Jasbani H.S.} and Sheila Wright and Megan Riddle and Celine Pourreyron and McMillan, {James R.} and Kimble, {Roy M.} and Marco Prisco and Ulrike Gartner and Emma Warbrick and {Irwin McLean}, {W. H.} and Leigh, {Irene M.} and McGrath, {John A.} and Salas-Alanis, {Julio C.} and Jakub Tolar and South, {Andrew P.}",
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Watt, SA, Dayal, JHS, Wright, S, Riddle, M, Pourreyron, C, McMillan, JR, Kimble, RM, Prisco, M, Gartner, U, Warbrick, E, Irwin McLean, WH, Leigh, IM, McGrath, JA, Salas-Alanis, JC, Tolar, J & South, AP 2015, 'Lysyl hydroxylase 3 localizes to epidermal basement membrane and is reduced in patients with recessive dystrophic epidermolysis bullosa', PLoS One, vol. 10, no. 9, e0137639. https://doi.org/10.1371/journal.pone.0137639

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; Irwin McLean, W. H.; Leigh, Irene M.; McGrath, John A.; Salas-Alanis, Julio C.; Tolar, Jakub; South, Andrew P.

In: PLoS One, Vol. 10, No. 9, e0137639, 18.09.2015.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Lysyl hydroxylase 3 localizes to epidermal basement membrane and is reduced in patients with recessive dystrophic epidermolysis bullosa

AU - Watt, Stephen A.

AU - Dayal, Jasbani H.S.

AU - Wright, Sheila

AU - Riddle, Megan

AU - Pourreyron, Celine

AU - McMillan, James R.

AU - Kimble, Roy M.

AU - Prisco, Marco

AU - Gartner, Ulrike

AU - Warbrick, Emma

AU - Irwin McLean, W. H.

AU - Leigh, Irene M.

AU - McGrath, John A.

AU - Salas-Alanis, Julio C.

AU - Tolar, Jakub

AU - South, Andrew P.

PY - 2015/9/18

Y1 - 2015/9/18

N2 - © 2015 Watt et al. 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.

AB - © 2015 Watt et al. 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.

U2 - 10.1371/journal.pone.0137639

DO - 10.1371/journal.pone.0137639

M3 - Article

VL - 10

JO - PLoS One

JF - PLoS One

SN - 1932-6203

IS - 9

M1 - e0137639

ER -