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Quantitative Methods to Study Protein Arginine Methyltransferase 1-9 Activity in Cells
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Quantitative Methods to Study Protein Arginine Methyltransferase 1-9 Activity in Cells

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Inhibition of the H3K4 methyltransferase SET7/9 ameliorates peritoneal fibrosis

Ryo Tamura1, Shigehiro Doi1, Ayumu Nakashima1

  • 1Department of Nephrology, Hiroshima University Hospital, Hiroshima, Japan.

Plos One
|May 4, 2018
PubMed

Insights

Inhibiting the SET7/9 enzyme reduces peritoneal fibrosis by decreasing H3K4me1 levels. This approach shows promise for treating fibrosis in patients undergoing peritoneal dialysis.

Area of Science:

  • Nephrology
  • Molecular Biology
  • Epigenetics

Background:

  • Transforming growth factor-β1 (TGF-β1) is a key factor in peritoneal fibrosis.
  • SET7/9, an H3K4 methyltransferase, influences fibrosis-related gene expression.
  • H3K4 mono-methylation (H3K4me1) by SET7/9 is crucial for activating these genes.

Purpose of the Study:

  • To investigate the impact of SET7/9 inhibition on peritoneal fibrosis.
  • To evaluate SET7/9 expression in mouse models and human peritoneal dialysis (PD) patients.
  • To explore the therapeutic potential of SET7/9 inhibition in ameliorating peritoneal fibrosis.

Main Methods:

  • Murine peritoneal fibrosis induced by methylglyoxal (MGO); treated with SET7/9 inhibitor sinefungin.
  • SET7/9 expression analyzed in mice and nonadherent cells from PD patient effluent.
  • Immunohistochemistry, peritoneal equilibration tests, and in vitro cell culture used.

Main Results:

  • Elevated SET7/9 expression observed in MGO-induced fibrosis and PD patients, correlating with creatinine transport.
  • Sinefungin suppressed mesenchymal cell markers, collagen deposition, and H3K4me1 levels.
  • Sinefungin attenuated urea and glucose transport rates and TGF-β1-induced fibrotic markers in vitro.

Conclusions:

  • SET7/9 inhibition ameliorates peritoneal fibrosis in mice.
  • SET7/9 is a potential therapeutic target for peritoneal fibrosis.
  • Inhibition of SET7/9 may improve outcomes for patients with peritoneal dialysis-related complications.

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