Abcc6 deficiency in mice leads to altered ABC transporter gene expression in metabolic active tissues 11 Medical and Health Sciences 1103 Clinical Sciences

Bettina Ibold, Isabel Faust, Janina Tiemann, Theo G. M. F. Gorgels, Arthur A. B. Bergen, Cornelius Knabbe, Doris Hendig

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

Background: ATP-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. Methods: The 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). Results: The 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. Conclusions: These 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.
Original languageEnglish
Article number2
JournalLipids in Health and Disease
Volume18
Issue number1
DOIs
Publication statusPublished - 2019

Cite this

Ibold, Bettina ; Faust, Isabel ; Tiemann, Janina ; Gorgels, Theo G. M. F. ; Bergen, Arthur A. B. ; Knabbe, Cornelius ; Hendig, Doris. / Abcc6 deficiency in mice leads to altered ABC transporter gene expression in metabolic active tissues 11 Medical and Health Sciences 1103 Clinical Sciences. In: Lipids in Health and Disease. 2019 ; Vol. 18, No. 1.
@article{a2bda46f17044ae9ad09cf236171fd94,
title = "Abcc6 deficiency in mice leads to altered ABC transporter gene expression in metabolic active tissues 11 Medical and Health Sciences 1103 Clinical Sciences",
abstract = "Background: ATP-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. Methods: The 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). Results: The 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. Conclusions: These 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.",
author = "Bettina Ibold and Isabel Faust and Janina Tiemann and Gorgels, {Theo G. M. F.} and Bergen, {Arthur A. B.} and Cornelius Knabbe and Doris Hendig",
year = "2019",
doi = "10.1186/s12944-018-0943-x",
language = "English",
volume = "18",
journal = "Lipids in Health and Disease",
issn = "1476-511X",
number = "1",

}

Abcc6 deficiency in mice leads to altered ABC transporter gene expression in metabolic active tissues 11 Medical and Health Sciences 1103 Clinical Sciences. / Ibold, Bettina; Faust, Isabel; Tiemann, Janina; Gorgels, Theo G. M. F.; Bergen, Arthur A. B.; Knabbe, Cornelius; Hendig, Doris.

In: Lipids in Health and Disease, Vol. 18, No. 1, 2, 2019.

Research output: Contribution to journalArticleAcademicpeer-review

TY - JOUR

T1 - Abcc6 deficiency in mice leads to altered ABC transporter gene expression in metabolic active tissues 11 Medical and Health Sciences 1103 Clinical Sciences

AU - Ibold, Bettina

AU - Faust, Isabel

AU - Tiemann, Janina

AU - Gorgels, Theo G. M. F.

AU - Bergen, Arthur A. B.

AU - Knabbe, Cornelius

AU - Hendig, Doris

PY - 2019

Y1 - 2019

N2 - Background: ATP-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. Methods: The 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). Results: The 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. Conclusions: These 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.

AB - Background: ATP-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. Methods: The 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). Results: The 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. Conclusions: These 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.

UR - https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=85059495916&origin=inward

UR - https://www.ncbi.nlm.nih.gov/pubmed/30611276

U2 - 10.1186/s12944-018-0943-x

DO - 10.1186/s12944-018-0943-x

M3 - Article

VL - 18

JO - Lipids in Health and Disease

JF - Lipids in Health and Disease

SN - 1476-511X

IS - 1

M1 - 2

ER -