Hendig, Doris and Langmann, Thomas and Kocken, Sarah and Zarbock, Ralf and Szliska, Christiane and Schmitz, Gerd and Kleesiek, Knut and Goetting, Christian (2008) Gene expression profiling of ABC transporters in dermal fibroblasts of pseudoxanthoma elasticum patients identifies new candidates involved in PXE pathogenesis. LABORATORY INVESTIGATION, 88 (12). pp. 1303-1315. ISSN 0023-6837,
Full text not available from this repository. (Request a copy)Abstract
Mutations in the ABCC6 gene, encoding the multidrug resistance-associated protein 6 (MRP6), cause pseudoxanthoma elasticum (PXE). This heritable disorder leads to pathological alterations in connective tissues. The implication of MRP6 deficiency in PXE is still unknown. Moreover, nothing is known about a possible compensatory expression of other ATP binding-cassette (ABC) transporter proteins in MRP6-deficient cells. We investigated the gene expression profile of 47 ABC transporters in human dermal fibroblasts of healthy controls (n = 2) and PXE patients (n = 4) by TaqMan low-density array. The analysis revealed the expression of 37 ABC transporter genes in dermal fibroblasts. ABCC6 gene expression was not quantifiable in fibroblasts derived from PXE patients. Seven genes (ABCA6, ABCA9, ABCA10, ABCB5, ABCC2, ABCC9 and ABCD2) were induced, whereas the gene expression of one gene (ABCA3) was decreased, comparing controls and PXE patients (with at least twofold changes). We reanalyzed the gene expression of selected ABC transporters in a larger set of dermal fibroblasts from controls and PXE patients (n = 6, each). Reanalysis showed high interindividual variability between samples, but confirmed the results obtained in the array analysis. The gene expression of ABC transporter genes, as well as lineage markers of PXE, was further examined after inhibition of ABCC6 gene expression by using specific small-interfering RNA. These experiments corroborated the observed gene expression alterations, most notably in the ABCA subclass (up to fourfold, P < 0.05). We therefore conclude that MRP6-deficient dermal fibroblasts exhibit a distinct gene expression profile of ABCA transporters, potentially to compensate for MRP6 deficiency. Moreover, our results point to a function for ABCC6/MRP6 in sterol transport, as sterols are preferential regulators of ABCA transporter activity and expression. Further studies are now required to uncover the role of ABCA transporters in PXE.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | MULTIDRUG-RESISTANCE PROTEIN-6; MATRIX-GLA-PROTEIN; ECTOPIC MINERALIZATION; CONNECTIVE TISSUES; TARGETED ABLATION; HDL CHOLESTEROL; TANGIER-DISEASE; MOUSE MODEL; IN-VITRO; MRP6; ABCC6; dermal fibroblast; gene expression profiling; MRP6; pseudoxanthoma elasticum; PXE |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Humangenetik Medicine > Lehrstuhl für Klinische Chemie und Laboratoriumsmedizin |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 16 Oct 2020 10:53 |
| Last Modified: | 16 Oct 2020 10:53 |
| URI: | https://pred.uni-regensburg.de/id/eprint/29996 |
Actions (login required)
 |
View Item |
