---
_id: '12984'
abstract:
- lang: eng
  text: "Background\r\nPseudoxanthoma elasticum (PXE) is a rare hereditary disorder
    characterized by late onset and progressive calcification of elastic fibers in
    skin, eyes and the cardiovascular system, exemplifying a model for conditions
    characterized by soft tissue calcification.\r\nObjective\r\nThe aim of our study
    was to characterize cellular inorganic pyrophosphate (PPi) homeostasis in PXE.\r\nMethods\r\nGene
    expression of PPi metabolizing enzymes was determined by quantitative real-time
    PCR after incubation up to 21 days with or without addition of Na2HPO4. Extracellular
    and cytosolic PPi concentrations were measured by enzyme-linked bioluminescence
    assay. ALP and ENPP1 activity was determined spectrophotometrically. We further
    established a human cell culture model suitable for investigating PXE and related
    disorders without addition of artificial calcification triggers.\r\nResults\r\nIndependently
    of the experimental conditions, PXE fibroblasts revealed a higher degree of matrix
    calcification. We observed that matrix calcification was associated with altered
    gene expression of PPi metabolizing enzymes in PXE fibroblasts. In this context,
    PXE fibroblasts exhibited significantly higher expression of ALP and OPN and reduced
    mRNA expression and activity of ENPP1. Here, for the first time cytosolic and
    extracellular PPi levels were shown to be strongly reduced in PXE fibroblasts.
    We further showed that PPi concentration in bovine and human sera additives had
    a strong impact on matrix calcification. In a last experimental line, we demonstrated
    that addition of PPi analogs reduced matrix calcification of PXE fibroblasts most
    likely by reducing ALP and OPN mRNA expression, restoring ENPP1 activity and subsequently
    elevating PPi concentrations.\r\nConclusion\r\nThe results of our study along
    with recent findings point to the essential role of PPi as the central regulatory
    metabolites preventing matrix calcification in PXE. But what remains to be determined
    is the underlying molecular mechanism leading to depletion of PPi in PXE. We further
    suggest that supplementation of PPi analogs might counteract pathological calcification
    in PXE and related disorders."
author:
- first_name: Mareike
  full_name: Dabisch-Ruthe, Mareike
  id: '66516'
  last_name: Dabisch-Ruthe
  orcid: https://orcid.org/0009-0008-7644-0826
- first_name: Patricia
  full_name: Kuzaj, Patricia
  last_name: Kuzaj
- first_name: Christian
  full_name: Götting, Christian
  last_name: Götting
- first_name: Cornelius
  full_name: Knabbe, Cornelius
  last_name: Knabbe
- first_name: Doris
  full_name: Hendig, Doris
  last_name: Hendig
citation:
  ama: Dabisch-Ruthe M, Kuzaj P, Götting C, Knabbe C, Hendig D. Pyrophosphates as
    a major inhibitor of matrix calcification in Pseudoxanthoma elasticum. <i>Journal
    of Dermatological Science</i>. 2014;75(2):109-120. doi:<a href="https://doi.org/10.1016/j.jdermsci.2014.04.015">10.1016/j.jdermsci.2014.04.015</a>
  apa: Dabisch-Ruthe, M., Kuzaj, P., Götting, C., Knabbe, C., &#38; Hendig, D. (2014).
    Pyrophosphates as a major inhibitor of matrix calcification in Pseudoxanthoma
    elasticum. <i>Journal of Dermatological Science</i>, <i>75</i>(2), 109–120. <a
    href="https://doi.org/10.1016/j.jdermsci.2014.04.015">https://doi.org/10.1016/j.jdermsci.2014.04.015</a>
  bjps: <b>Dabisch-Ruthe M <i>et al.</i></b> (2014) Pyrophosphates as a Major Inhibitor
    of Matrix Calcification in Pseudoxanthoma Elasticum. <i>Journal of Dermatological
    Science</i> <b>75</b>, 109–120.
  chicago: 'Dabisch-Ruthe, Mareike, Patricia Kuzaj, Christian Götting, Cornelius Knabbe,
    and Doris Hendig. “Pyrophosphates as a Major Inhibitor of Matrix Calcification
    in Pseudoxanthoma Elasticum.” <i>Journal of Dermatological Science</i> 75, no.
    2 (2014): 109–20. <a href="https://doi.org/10.1016/j.jdermsci.2014.04.015">https://doi.org/10.1016/j.jdermsci.2014.04.015</a>.'
  chicago-de: 'Dabisch-Ruthe, Mareike, Patricia Kuzaj, Christian Götting, Cornelius
    Knabbe und Doris Hendig. 2014. Pyrophosphates as a major inhibitor of matrix calcification
    in Pseudoxanthoma elasticum. <i>Journal of Dermatological Science</i> 75, Nr.
    2: 109–120. doi:<a href="https://doi.org/10.1016/j.jdermsci.2014.04.015">10.1016/j.jdermsci.2014.04.015</a>,
    .'
  din1505-2-1: '<span style="font-variant:small-caps;">Dabisch-Ruthe, Mareike</span>
    ; <span style="font-variant:small-caps;">Kuzaj, Patricia</span> ; <span style="font-variant:small-caps;">Götting,
    Christian</span> ; <span style="font-variant:small-caps;">Knabbe, Cornelius</span>
    ; <span style="font-variant:small-caps;">Hendig, Doris</span>: Pyrophosphates
    as a major inhibitor of matrix calcification in Pseudoxanthoma elasticum. In:
    <i>Journal of Dermatological Science</i> Bd. 75. Amsterdam, Elsevier  (2014),
    Nr. 2, S. 109–120'
  havard: M. Dabisch-Ruthe, P. Kuzaj, C. Götting, C. Knabbe, D. Hendig, Pyrophosphates
    as a major inhibitor of matrix calcification in Pseudoxanthoma elasticum, Journal
    of Dermatological Science. 75 (2014) 109–120.
  ieee: 'M. Dabisch-Ruthe, P. Kuzaj, C. Götting, C. Knabbe, and D. Hendig, “Pyrophosphates
    as a major inhibitor of matrix calcification in Pseudoxanthoma elasticum,” <i>Journal
    of Dermatological Science</i>, vol. 75, no. 2, pp. 109–120, 2014, doi: <a href="https://doi.org/10.1016/j.jdermsci.2014.04.015">10.1016/j.jdermsci.2014.04.015</a>.'
  mla: Dabisch-Ruthe, Mareike, et al. “Pyrophosphates as a Major Inhibitor of Matrix
    Calcification in Pseudoxanthoma Elasticum.” <i>Journal of Dermatological Science</i>,
    vol. 75, no. 2, 2014, pp. 109–20, <a href="https://doi.org/10.1016/j.jdermsci.2014.04.015">https://doi.org/10.1016/j.jdermsci.2014.04.015</a>.
  short: M. Dabisch-Ruthe, P. Kuzaj, C. Götting, C. Knabbe, D. Hendig, Journal of
    Dermatological Science 75 (2014) 109–120.
  ufg: '<b>Dabisch-Ruthe, Mareike u. a.</b>: Pyrophosphates as a major inhibitor of
    matrix calcification in Pseudoxanthoma elasticum, in: <i>Journal of Dermatological
    Science</i> 75 (2014), H. 2,  S. 109–120.'
  van: Dabisch-Ruthe M, Kuzaj P, Götting C, Knabbe C, Hendig D. Pyrophosphates as
    a major inhibitor of matrix calcification in Pseudoxanthoma elasticum. Journal
    of Dermatological Science. 2014;75(2):109–20.
date_created: 2025-06-17T06:52:59Z
date_updated: 2025-06-17T13:48:41Z
department:
- _id: DEP4010
doi: 10.1016/j.jdermsci.2014.04.015
intvolume: '        75'
issue: '2'
keyword:
- Pseudoxanthoma elasticum
- Calcification
- Pyrophosphate
- Bisphosphonate
- ABCC6
- Tissue nonspecific alkaline phosphate
- Ectonucleotide pyrophosphatase 1
language:
- iso: eng
page: 109-120
place: Amsterdam
publication: Journal of Dermatological Science
publication_identifier:
  eissn:
  - 1873-569X
  issn:
  - 0923-1811
publication_status: published
publisher: 'Elsevier '
quality_controlled: '1'
status: public
title: Pyrophosphates as a major inhibitor of matrix calcification in Pseudoxanthoma
  elasticum
type: scientific_journal_article
user_id: '83781'
volume: 75
year: '2014'
...
---
_id: '12986'
abstract:
- lang: eng
  text: "Background\r\nDysregulations in cholesterol and lipid metabolism have been
    linked to human diseases like hypercholesterolemia, atherosclerosis or the metabolic
    syndrome. Many ABC transporters are involved in trafficking of metabolites derived
    from these pathways. Pseudoxanthoma elasticum (PXE), an autosomal-recessive disease
    caused by ABCC6 mutations, is characterized by atherogenesis and soft tissue calcification.\r\nMethods\r\nIn
    this study we investigated the regulation of cholesterol biosynthesis in human
    dermal fibroblasts from PXE patients and healthy controls.\r\nResults\r\nGene
    expression analysis of 84 targets indicated dysregulations in cholesterol metabolism
    in PXE fibroblasts. Transcript levels of ABCC6 were strongly increased in lipoprotein-deficient
    serum (LPDS) and under serum starvation in healthy controls. For the first time,
    increased HMG CoA reductase activities were found in PXE fibroblasts. We further
    observed strongly elevated transcript and protein levels for the proprotein convertase
    subtilisin/kexin type 9 (PCSK9), as well as a significant reduction in APOE mRNA
    expression in PXE.\r\nConclusion\r\nIncreased cholesterol biosynthesis, elevated
    PCSK9 levels and reduced APOE mRNA expression newly found in PXE fibroblasts could
    enforce atherogenesis and cardiovascular risk in PXE patients. Moreover, the increase
    in ABCC6 expression accompanied by the induction of cholesterol biosynthesis supposes
    a functional role for ABCC6 in human lipoprotein and cholesterol homeostasis."
article_number: '118'
author:
- first_name: Patricia
  full_name: Kuzaj, Patricia
  last_name: Kuzaj
- first_name: Joachim
  full_name: Kuhn, Joachim
  last_name: Kuhn
- first_name: Mareike
  full_name: Dabisch-Ruthe, Mareike
  id: '66516'
  last_name: Dabisch-Ruthe
  orcid: https://orcid.org/0009-0008-7644-0826
- first_name: Isabel
  full_name: Faust, Isabel
  last_name: Faust
- first_name: Christian
  full_name: Götting, Christian
  last_name: Götting
- first_name: Cornelius
  full_name: Knabbe, Cornelius
  last_name: Knabbe
- first_name: Doris
  full_name: Hendig, Doris
  last_name: Hendig
citation:
  ama: Kuzaj P, Kuhn J, Dabisch-Ruthe M, et al. ABCC6- a new player in cellular cholesterol
    and lipoprotein metabolism? <i>Lipids in Health and Disease</i>. 2014;13(1). doi:<a
    href="https://doi.org/10.1186/1476-511x-13-118">10.1186/1476-511x-13-118</a>
  apa: Kuzaj, P., Kuhn, J., Dabisch-Ruthe, M., Faust, I., Götting, C., Knabbe, C.,
    &#38; Hendig, D. (2014). ABCC6- a new player in cellular cholesterol and lipoprotein
    metabolism? <i>Lipids in Health and Disease</i>, <i>13</i>(1), Article 118. <a
    href="https://doi.org/10.1186/1476-511x-13-118">https://doi.org/10.1186/1476-511x-13-118</a>
  bjps: <b>Kuzaj P <i>et al.</i></b> (2014) ABCC6- a New Player in Cellular Cholesterol
    and Lipoprotein Metabolism? <i>Lipids in Health and Disease</i> <b>13</b>.
  chicago: Kuzaj, Patricia, Joachim Kuhn, Mareike Dabisch-Ruthe, Isabel Faust, Christian
    Götting, Cornelius Knabbe, and Doris Hendig. “ABCC6- a New Player in Cellular
    Cholesterol and Lipoprotein Metabolism?” <i>Lipids in Health and Disease</i> 13,
    no. 1 (2014). <a href="https://doi.org/10.1186/1476-511x-13-118">https://doi.org/10.1186/1476-511x-13-118</a>.
  chicago-de: Kuzaj, Patricia, Joachim Kuhn, Mareike Dabisch-Ruthe, Isabel Faust,
    Christian Götting, Cornelius Knabbe und Doris Hendig. 2014. ABCC6- a new player
    in cellular cholesterol and lipoprotein metabolism? <i>Lipids in Health and Disease</i>
    13, Nr. 1. doi:<a href="https://doi.org/10.1186/1476-511x-13-118">10.1186/1476-511x-13-118</a>,
    .
  din1505-2-1: '<span style="font-variant:small-caps;">Kuzaj, Patricia</span> ; <span
    style="font-variant:small-caps;">Kuhn, Joachim</span> ; <span style="font-variant:small-caps;">Dabisch-Ruthe,
    Mareike</span> ; <span style="font-variant:small-caps;">Faust, Isabel</span> ;
    <span style="font-variant:small-caps;">Götting, Christian</span> ; <span style="font-variant:small-caps;">Knabbe,
    Cornelius</span> ; <span style="font-variant:small-caps;">Hendig, Doris</span>:
    ABCC6- a new player in cellular cholesterol and lipoprotein metabolism? In: <i>Lipids
    in Health and Disease</i> Bd. 13. London, Biomed Central  (2014), Nr. 1'
  havard: P. Kuzaj, J. Kuhn, M. Dabisch-Ruthe, I. Faust, C. Götting, C. Knabbe, D.
    Hendig, ABCC6- a new player in cellular cholesterol and lipoprotein metabolism?,
    Lipids in Health and Disease. 13 (2014).
  ieee: 'P. Kuzaj <i>et al.</i>, “ABCC6- a new player in cellular cholesterol and
    lipoprotein metabolism?,” <i>Lipids in Health and Disease</i>, vol. 13, no. 1,
    Art. no. 118, 2014, doi: <a href="https://doi.org/10.1186/1476-511x-13-118">10.1186/1476-511x-13-118</a>.'
  mla: Kuzaj, Patricia, et al. “ABCC6- a New Player in Cellular Cholesterol and Lipoprotein
    Metabolism?” <i>Lipids in Health and Disease</i>, vol. 13, no. 1, 118, 2014, <a
    href="https://doi.org/10.1186/1476-511x-13-118">https://doi.org/10.1186/1476-511x-13-118</a>.
  short: P. Kuzaj, J. Kuhn, M. Dabisch-Ruthe, I. Faust, C. Götting, C. Knabbe, D.
    Hendig, Lipids in Health and Disease 13 (2014).
  ufg: '<b>Kuzaj, Patricia u. a.</b>: ABCC6- a new player in cellular cholesterol
    and lipoprotein metabolism?, in: <i>Lipids in Health and Disease</i> 13 (2014),
    H. 1.'
  van: Kuzaj P, Kuhn J, Dabisch-Ruthe M, Faust I, Götting C, Knabbe C, et al. ABCC6-
    a new player in cellular cholesterol and lipoprotein metabolism? Lipids in Health
    and Disease. 2014;13(1).
date_created: 2025-06-17T06:53:58Z
date_updated: 2025-06-17T13:49:15Z
department:
- _id: DEP4010
doi: 10.1186/1476-511x-13-118
intvolume: '        13'
issue: '1'
keyword:
- Pseudoxanthoma elasticum
- ABC transporter
- ABCC6
- Cholesterol biosynthesis
- Atherosclerosis
- HMG CoA reductase
- SREBP2
- PCSK9
- LDLR
- APOE
language:
- iso: eng
place: London
publication: Lipids in Health and Disease
publication_identifier:
  eissn:
  - 1476-511X
publication_status: published
publisher: 'Biomed Central '
quality_controlled: '1'
status: public
title: ABCC6- a new player in cellular cholesterol and lipoprotein metabolism?
type: scientific_journal_article
user_id: '83781'
volume: 13
year: '2014'
...