Open Access

High glucose induces podocyte epithelial‑to‑mesenchymal transition by demethylation‑mediated enhancement of MMP9 expression

  • Authors:
    • Li Ling
    • Libo Chen
    • Changning Zhang
    • Shuyan Gui
    • Haiyan Zhao
    • Zhengzhang Li
  • View Affiliations

  • Published online on: February 2, 2018     https://doi.org/10.3892/mmr.2018.8554
  • Pages: 5642-5651
  • Copyright: © Ling et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Abnormal expression of matrix metalloproteinase 9 (MMP9) is correlated with podocyte epithelial-to-­­mesenchymal transition (EMT) in diabetic nephropathy (DN). However, the mechanisms underlying this process are not well defined. Site‑specific demethylation may sustain high expression levels of target genes. In the present study, in order to investigate the association between DNA demethylation of MMP9 promoter and podocyte EMT in DN, human podocytes were cultured in high‑glucose (HG) medium and a rat model of DN was established by intraperitoneal injection of streptozotocin (STZ) to determine whether site‑specific demethylation of the MMP9 promoter was involved in regulating podocyte EMT in DN. The MTT assay was used to assess the effects of HG culture on the growth of podocytes, and the demethylation status of the MMP9 promoter was assessed by bisulfite sequencing polymerase chain reaction. mRNA and protein expression levels of MMP9, α‑smooth muscle actin (α‑SMA), podocalyxin and fibronectin‑1 in podocytes were assessed by reverse transcription‑quantitative PCR (RT‑qPCR) and western blot analyses. The results demonstrated that HG treatment up regulated the expression of MMP9, α‑SMA and fibronectin‑1, but down regulated the expression of podocalyxin in podocytes. The MMP9 promoter region was revealed to contain a variety of demethylated CpG sites, and HG treatment reduced the rate of MMP9 promotermethylation, which, in turn, enhanced its promoter activity. In summary, these data suggested that demethylation of the MMP9 promoter may serve an important role in podocyte EMT in DN. The demethylation status of the MMP9 promoter maybe used as an important prognostic marker of DN in clinic.
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April-2018
Volume 17 Issue 4

Print ISSN: 1791-2997
Online ISSN:1791-3004

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Spandidos Publications style
Ling L, Chen L, Zhang C, Gui S, Zhao H and Li Z: High glucose induces podocyte epithelial‑to‑mesenchymal transition by demethylation‑mediated enhancement of MMP9 expression. Mol Med Rep 17: 5642-5651, 2018.
APA
Ling, L., Chen, L., Zhang, C., Gui, S., Zhao, H., & Li, Z. (2018). High glucose induces podocyte epithelial‑to‑mesenchymal transition by demethylation‑mediated enhancement of MMP9 expression. Molecular Medicine Reports, 17, 5642-5651. https://doi.org/10.3892/mmr.2018.8554
MLA
Ling, L., Chen, L., Zhang, C., Gui, S., Zhao, H., Li, Z."High glucose induces podocyte epithelial‑to‑mesenchymal transition by demethylation‑mediated enhancement of MMP9 expression". Molecular Medicine Reports 17.4 (2018): 5642-5651.
Chicago
Ling, L., Chen, L., Zhang, C., Gui, S., Zhao, H., Li, Z."High glucose induces podocyte epithelial‑to‑mesenchymal transition by demethylation‑mediated enhancement of MMP9 expression". Molecular Medicine Reports 17, no. 4 (2018): 5642-5651. https://doi.org/10.3892/mmr.2018.8554