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Int J Mol Sci. 2017 Sep 11;18(9). pii: E1941. doi: 10.3390/ijms18091941.

The ABCC6 Transporter: A New Player in Biomineralization.

Author information

1
FINSERM, U 1081, Aging and Diabetes Team, Institute for Research on Cancer and Aging of Nice (IRCAN), 06107 Nice, France. avre.g@chu-nice.fr.
2
CNRS, UMR7284, Institute for Research on Cancer and Aging of Nice (IRCAN), 06107 Nice, France. avre.g@chu-nice.fr.
3
Faculty of Medicine, University of Nice-Sophia Antipolis, 06107 Nice, France. avre.g@chu-nice.fr.
4
Nephrology Department, University Hospital, 06107 Nice, France. avre.g@chu-nice.fr.
5
Nephrology Department, University Hospital, 06107 Nice, France. a.laurain@live.fr.
6
Institute of Enzymology, Research Centre for Natural Sciences, Hungarian Academy of Sciences, 1117 Budapest, Hungary. aranyi.tamas@ttk.mta.hu.
7
Institute of Enzymology, Research Centre for Natural Sciences, Hungarian Academy of Sciences, 1117 Budapest, Hungary. floraszeri@me.com.
8
Institute of Enzymology, Research Centre for Natural Sciences, Hungarian Academy of Sciences, 1117 Budapest, Hungary. fulop.krisztina@ttk.mta.hu.
9
Department Cell and Molecular Biology, John A. Burns School of Medicine, University of Hawaii, Honolulu, HI 96813, USA. lesaux@hawaii.edu.
10
Laboratory of Physiology and Molecular Medicine (LP2M) UMR CNRS 7073, 06107 Nice, France. duranton@unice.fr.
11
UMR CNRS 6015-Inserm 1083, School of Medicine, Bretagne Loire University, 49045 Angers, France. gilles.kauffenstein@gmail.com.
12
PXE Health and Research Center, University Hospital of Angers, 49045 Angers, France. gilles.kauffenstein@gmail.com.
13
UMR CNRS 6015-Inserm 1083, School of Medicine, Bretagne Loire University, 49045 Angers, France. LuMartin@chu-angers.fr.
14
PXE Health and Research Center, University Hospital of Angers, 49045 Angers, France. LuMartin@chu-angers.fr.
15
Faculty of Medicine, University of Nice-Sophia Antipolis, 06107 Nice, France. leftheriotis.g@chu-nice.fr.
16
Laboratory of Physiology and Molecular Medicine (LP2M) UMR CNRS 7073, 06107 Nice, France. leftheriotis.g@chu-nice.fr.

Abstract

Pseudoxanthoma elasticum (PXE) is an inherited metabolic disease with autosomal recessive inheritance caused by mutations in the ABCC6 gene. Since the first description of the disease in 1896, alleging a disease involving the elastic fibers, the concept evolved with the further discoveries of the pivotal role of ectopic mineralization that is preponderant in the elastin-rich tissues of the skin, eyes and blood vessel walls. After discovery of the causative gene of the disease in 2000, the function of the ABCC6 protein remains elusive. More than 300 mutations have been now reported and the concept of a dermal disease has progressively evolved toward a metabolic disorder resulting from the remote effects caused by lack of a circulating anti-mineralization factor. Very recently, evidence has accumulated that this anti-mineralizing factor is inorganic pyrophosphate (PPi). This leads to decreased PPi/Pi (inorganic phosphate) ratio that results from the lack of extracellular ATP release by hepatocytes and probably renal cells harboring the mutant ABCC6 protein. However, the mechanism by which ABCC6 dysfunction causes diminished ATP release remains an enigma. Studies of other ABC transporters, such as ABCC7 or ABCC1 could help our understanding of what ABCC6 exact function is. Data and a hypothesis on the possible roles of ABCC6 in acquired metabolic diseases are also discussed.

KEYWORDS:

ABC transporter; arterial calcifications; chronic kidney disease; inorganic pyrophosphate; pseudoxanthoma elasticum

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