Pseudoxanthoma Elasticum: Progress in Research Toward Treatment: Summary of the 2012 PXE International Research Meeting

Uitto, Jouni; Váradi, András; Bercovitch, Lionel; Terry, Patrick F.; Terry, Sharon F.

doi:10.1038/jid.2013.20

Cited by 67 publications

(81 citation statements)

References 37 publications

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“…This prototypical connective tissue disease affects ∼1 in 50,000 persons worldwide, for whom there is no effective therapy (2). Along with relatively benign (but stigmatizing) skin lesions, PXE causes progressive loss of vision and cardiovascular complications (2).…”

mentioning

confidence: 99%

ABCC6 prevents ectopic mineralization seen in pseudoxanthoma elasticum by inducing cellular nucleotide release

Jansen

Küçükosmanoğlu

Haas

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

235

310

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Pseudoxanthoma elasticum (PXE) is an autosomal recessive disease characterized by progressive ectopic mineralization of the skin, eyes, and arteries, for which no effective treatment exists. PXE is caused by inactivating mutations in the gene encoding ATPbinding cassette sub-family C member 6 (ABCC6), an ATP-dependent efflux transporter present mainly in the liver. Abcc6 −/− mice have been instrumental in demonstrating that PXE is a metabolic disease caused by the absence of an unknown factor in the circulation, the presence of which depends on ABCC6 in the liver. Why absence of this factor results in PXE has remained a mystery. Here we report that medium from HEK293 cells overexpressing either human or rat ABCC6 potently inhibits mineralization in vitro, whereas medium from HEK293 control cells does not. Untargeted metabolomics revealed that cells expressing ABCC6 excrete large amounts of nucleoside triphosphates, even though ABCC6 itself does not transport nucleoside triphosphates. Extracellularly, ectonucleotidases hydrolyze the excreted nucleoside triphosphates to nucleoside monophosphates and inorganic pyrophosphate (PPi), a strong inhibitor of mineralization that plays a pivotal role in several mineralization disorders similar to PXE. The in vivo relevance of our data are demonstrated in Abcc6 −/− mice, which had plasma PPi levels <40% of those found in WT mice. This study provides insight into how ABCC6 affects PXE. Our data indicate that the factor that normally prevents PXE is PPi, which is provided to the circulation in the form of nucleoside triphosphates via an asyet unidentified but ABCC6-dependent mechanism.ATP secretion | ectopic calcification | MRP6 | ENPP1

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mentioning

confidence: 99%

ABCC6 prevents ectopic mineralization seen in pseudoxanthoma elasticum by inducing cellular nucleotide release

Jansen

Küçükosmanoğlu

Haas

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

235

310

View full text Add to dashboard Cite

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“…Retinal hemorajiyi önlemek için hastanın kafa travması ve ağır yük kaldırmadan kaçınması gerekir. Tedavide, koroidal neovaskülarizasyon için lazer uygulanır (8,13). Neovaskülarizasyonu önlemek için, vasküler endotelyal büyüme faktörü antagonistlerinin vitreus içine enjeksiyonu faydalı bulunmuştur (11).…”

Section: Discussionunclassified

“…Tedavide, koroidal neovaskülarizasyon için lazer uygulanır (8,13). Neovaskülarizasyonu önlemek için, vasküler endotelyal büyüme faktörü antagonistlerinin vitreus içine enjeksiyonu faydalı bulunmuştur (11). Çalışma aşamasında olan tedaviler arasında yer alan fosfat bağlayıcıların yararlı olduğu ifade edilmiştir (8,13).…”

Section: Discussionunclassified

“…Neovaskülarizasyonu önlemek için, vasküler endotelyal büyüme faktörü antagonistlerinin vitreus içine enjeksiyonu faydalı bulunmuştur (11). Çalışma aşamasında olan tedaviler arasında yer alan fosfat bağlayıcıların yararlı olduğu ifade edilmiştir (8,13). Mineralizasyonun önüne geçmek için diyette magnezyumu arttırmak üzerine deneyler yapılmaktadır, faydalı olduğuna dair yayınlar mevcuttur (11).…”

Section: Discussionunclassified

“…Çalışma aşamasında olan tedaviler arasında yer alan fosfat bağlayıcıların yararlı olduğu ifade edilmiştir (8,13). Mineralizasyonun önüne geçmek için diyette magnezyumu arttırmak üzerine deneyler yapılmaktadır, faydalı olduğuna dair yayınlar mevcuttur (11). ABCC6 geninde PTC124 aracılığıyla saçma mutasyonların oluşturulmasını tedavi için öneren çalışmalar bulunmaktadır (14).…”

Section: Discussionunclassified

See 2 more Smart Citations

Pseudoxanthoma Elasticum: A Pediatric Case

Çoban¹,

Ergin²,

Taşlı³

et al. 2015

tdd

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The Human Face of ABCC6

Terry

2020

FEBS Letters

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Researchers working on basic and translational clinical science related to ABC transporters are enthusiastic and dedicated investigators. As the field has grown, so has its contribution to human disease. Pseudoxanthoma elasticum (PXE) International, an advocacy organization established by non-scientists, began supporting research and convenings on these transporters, specifically ABCC6, the gene associated with PXE, 20 years ago. As a patient advocacy organization, we have spent more than 25 years creating a large research consortium, initiating, funding and conducting research. Years of basic modelling and vigorous hypothesis testing have resulted in some important advances leading to clinical trials. The synergy of basic scientists, lay advocates, clinicians and translational scientists has dramatically accelerated research on PXE and progress towards better and more effective treatments for PXE patients.

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Pseudoxanthoma Elasticum: Progress in Research Toward Treatment: Summary of the 2012 PXE International Research Meeting

Cited by 67 publications

References 37 publications

ABCC6 prevents ectopic mineralization seen in pseudoxanthoma elasticum by inducing cellular nucleotide release

ABCC6 prevents ectopic mineralization seen in pseudoxanthoma elasticum by inducing cellular nucleotide release

Pseudoxanthoma Elasticum: A Pediatric Case

The Human Face of ABCC6

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