View : 19 Download: 3

Substrate-specific gene expression profiles in different kidney cell types are associated with Fabry disease

Title
Substrate-specific gene expression profiles in different kidney cell types are associated with Fabry disease
Authors
Shin, Youn-JeongJeon, Yeo JinJung, NamheePark, Joo-WonPark, Hae-YoungJung, Sung-Chul
Ewha Authors
박혜영정성철박주원
SCOPUS Author ID
박혜영scopus; 정성철scopus; 박주원scopus
Issue Date
2015
Journal Title
MOLECULAR MEDICINE REPORTS
ISSN
1791-2997JCR Link1791-3004JCR Link
Citation
vol. 12, no. 4, pp. 5049 - 5057
Keywords
Fabry diseasekidneyglobotriaosylceramideglobotriaosylsphingosinegene expression profilemesangial cellepithelial cell
Publisher
SPANDIDOS PUBL LTD
Indexed
SCIE; SCOPUS WOS scopus
Abstract
Fabry disease is an X-linked lysosomal storage disorder caused by mutations in the gene encoding the a-galactosidase A (alpha-Gal A) lysosomal enzyme, which results in globotriaosylceramide (Gb3) storage in vascular endothelial cells and different cell types throughout the body. Involvement of the kidney and heart is life threatening, and fibrosis of these organs is considered to be involved in the pathogenesis of Fabry disease. An increased concentration of deacylated Gb3 (lyso-Gb3) in the plasma of symptomatic patients has also been suggested as a causative molecular event. To elucidate the molecular mechanisms involved in renal fibrosis in Fabry disease, the present analyzed the changes in global gene expression prior to and following Gb3 or lyso-Gb3 treatment in two types of kidney cell lines, human proximal renal tubular epithelial (HK-2) and mouse renal glomerular mesangial (SV40 MES 13) cells. Gb3 and lyso-Gb3 treatment regulated the expression of 199 and 328 genes in each cell type, demonstrating a >2.0-fold change. The majority of the biological functions of the regulated genes were associated with fibrogenesis or epithelial-mesenchymal transition (EMT). The gene expression patterns of sphingolipid-treated HK-2 cells were distinguishable from the patterns in the SV40 MES 13 cells. Several genes associated with the EMT were selected and evaluated further in kidney cells and in Fabry mouse kidney tissues. In the SV40 MES 13 cells, the DLL1, F8, and HOXA11 genes were downregulated, and FOXP2 was upregulated by treatment with Gb3 or lyso-Gb3. In the HK-2 cells, the ADAMTS6, BEST1, IL4, and MYH11 genes were upregulated. Upregulation of the FOXP2, COL15A1,IL4, and MYH11 genes was also observed in the Fabry mouse kidney tissues. The gene expression profiles in kidney cells following the addition of Gb3 or lyso-Gb3 revealed substrate-specific and cell-specific patterns. These findings suggested that Gb3 and lyso-Gb3 lead to renal fibrosis in Fabry disease through different biochemical modulations.
DOI
10.3892/mmr.2015.4010
Appears in Collections:
의학전문대학원 > 의학과 > Journal papers
Files in This Item:
001.pdf(699.76 kB)Download
Export
RIS (EndNote)
XLS (Excel)
XML


qrcode

Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.

BROWSE