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

  • Authors:
    • Youn‑Jeong Shin
    • Yeo Jin Jeon
    • Namhee Jung
    • Joo‑Won Park
    • Hae‑Young Park
    • Sung‑Chul Jung
  • View Affiliations / Copyright

    Affiliations: Department of Biochemistry, School of Medicine, Ewha Womans University, Seoul 158‑710, Republic of Korea
    Copyright: © Shin et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Pages: 5049-5057
    |
    Published online on: July 1, 2015
       https://doi.org/10.3892/mmr.2015.4010
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Abstract

Fabry disease is an X-linked lysosomal storage disorder caused by mutations in the gene encoding the α-galactosidase A (α-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.
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Copy and paste a formatted citation
Spandidos Publications style
Shin YJ, Jeon YJ, Jung N, Park JW, Park HY and Jung SC: Substrate-specific gene expression profiles in different kidney cell types are associated with Fabry disease. Mol Med Rep 12: 5049-5057, 2015.
APA
Shin, Y., Jeon, Y.J., Jung, N., Park, J., Park, H., & Jung, S. (2015). Substrate-specific gene expression profiles in different kidney cell types are associated with Fabry disease. Molecular Medicine Reports, 12, 5049-5057. https://doi.org/10.3892/mmr.2015.4010
MLA
Shin, Y., Jeon, Y. J., Jung, N., Park, J., Park, H., Jung, S."Substrate-specific gene expression profiles in different kidney cell types are associated with Fabry disease". Molecular Medicine Reports 12.4 (2015): 5049-5057.
Chicago
Shin, Y., Jeon, Y. J., Jung, N., Park, J., Park, H., Jung, S."Substrate-specific gene expression profiles in different kidney cell types are associated with Fabry disease". Molecular Medicine Reports 12, no. 4 (2015): 5049-5057. https://doi.org/10.3892/mmr.2015.4010
Copy and paste a formatted citation
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Spandidos Publications style
Shin YJ, Jeon YJ, Jung N, Park JW, Park HY and Jung SC: Substrate-specific gene expression profiles in different kidney cell types are associated with Fabry disease. Mol Med Rep 12: 5049-5057, 2015.
APA
Shin, Y., Jeon, Y.J., Jung, N., Park, J., Park, H., & Jung, S. (2015). Substrate-specific gene expression profiles in different kidney cell types are associated with Fabry disease. Molecular Medicine Reports, 12, 5049-5057. https://doi.org/10.3892/mmr.2015.4010
MLA
Shin, Y., Jeon, Y. J., Jung, N., Park, J., Park, H., Jung, S."Substrate-specific gene expression profiles in different kidney cell types are associated with Fabry disease". Molecular Medicine Reports 12.4 (2015): 5049-5057.
Chicago
Shin, Y., Jeon, Y. J., Jung, N., Park, J., Park, H., Jung, S."Substrate-specific gene expression profiles in different kidney cell types are associated with Fabry disease". Molecular Medicine Reports 12, no. 4 (2015): 5049-5057. https://doi.org/10.3892/mmr.2015.4010
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