Abstract
BackgroundATP-binding cassette (ABC) transporters are involved in a huge range of physiological processes. Mutations in the ABCC6 gene cause pseudoxanthoma elasticum, a metabolic disease with progressive soft tissue calcification.MethodsThe aim of the present study was to analyze gene expression levels of selected ABC transporters associated with cholesterol homeostasis in metabolic active tissues, such as the liver, kidney and white adipose tissue (WAT) of Abcc6−/− mice from an early and late disease stage (six-month-old and 12-month-old mice).ResultsThe strongest regulation of ABC transporter genes was observed in the liver tissue of six-month-old Abcc6−/− mice. Here, we found a significant increase of mRNA expression levels of phospholipid, bile salt and cholesterol/sterol transporters Abcb1b, Abcb11, Abcg1, Abcg5 and Abcg8. Abcd2 mRNA expression was increased by 3.2-fold in the liver tissue. We observed strong upregulation of Abca3 and Abca1 mRNA expression up to 3.3-fold in kidney and WAT, and a 2-fold increase of Abca9 mRNA in the WAT of six-month-old Abcc6 knockout mice. Gene expression levels of Abcb1b and Abcg1 remained increased in the liver tissue after an age-related disease progression, while we observed lower mRNA expression of Abca3 and Abca9 in the kidney and WAT of 12-month-old Abcc6−/− mice.ConclusionsThese data support previous findings that Abcc6 deficiency leads to an altered gene expression of other ABC transporters depending on the status of disease progression. The increased expression of fatty acid, bile salt and cholesterol/sterol transporters may be linked to an altered cholesterol and lipoprotein metabolism due to a loss of Abcc6 function.
Highlights
Adenosine triphosphate (ATP)-binding cassette (ABC) transporters are involved in a huge range of physiological processes
We have examined the expression profile of selected ATP-binding cassette (ABC) transporter genes associated with cholesterol homeostasis [9,10,11] in Abcc6−/− mice compared to wild type (WT) mice, because there are several indications that pseudoxanthoma elasticum (PXE) is linked to an alteration of cholesterol metabolism accompanied by altered ABC transporter gene expression [8, 12, 13]
The mRNA expression profiles were compared between Abcc6−/− mice and age-matched WT mice to examine the effects of Abcc6 deficiency on gene expression levels of other ABC transporters
Summary
ATP-binding cassette (ABC) transporters are involved in a huge range of physiological processes. Eukaryotic members of the ATP-binding cassette (ABC) superfamily mediate the export of a wide range of substrates and have, a functional importance in various physiological processes. These transporter proteins use ATP hydrolysis to move the respective substrate against their concentration gradient. The ABC transporters are grouped into seven subfamilies depending on (2019) 18:2 disease, which is characterized by progressive calcification of connective tissue and manifests in early adolescence. Ectopic mineralization of blood vessels first occurs in six-month-old Abcc6−/− mice in many tissues and progresses with age [8]
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