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Mechanism of Kemeng Fang's Inhibition of Podocyte Apoptosis in Rats with Membranous Nephropathy through the PI3K/AKT Signaling Pathway
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DNMT3a negatively regulates PTEN to activate the PI3K/AKT pathway to aggravate renal fibrosis

Taotao Hu1, Fang Chen1, Dan Chen1

  • 1Department of Nephrology, Wuhan No.1 Hospital, Wuhan, 430022, China.

Cellular Signalling
|May 6, 2022
PubMed
Abstract

Insights

PTEN methylation is linked to renal fibrosis. DNMT3a downregulates PTEN, activating the PI3K/AKT pathway and worsening kidney fibrosis through epithelial-mesenchymal transition.

Area of Science:

  • Nephrology
  • Molecular Biology
  • Epigenetics

Background:

  • Renal fibrosis is a significant global health concern.
  • PTEN methylation is implicated in fibrotic diseases, but its role in renal fibrosis is unclear.

Purpose of the Study:

  • To investigate the role of PTEN methylation in renal fibrosis.
  • To elucidate the mechanism by which PTEN methylation regulates renal fibrosis.

Main Methods:

  • Established unilateral ureteral obstruction (UUO) mouse and TGF-β1-stimulated HK-2 cell models.
  • Assessed fibrosis using HE and Masson's trichrome staining.
  • Analyzed PTEN expression, methylation (MSP), and interaction with DNMT3a (ChIP-qRT-PCR).

Main Results:

  • PTEN promoter methylation and reduced PTEN expression were observed in UUO models.
  • Demethylation inhibited epithelial-mesenchymal transition (EMT) and renal fibrosis.
  • DNMT3a knockdown reversed TGF-β1-induced PTEN inhibition and activated PI3K/AKT signaling.

Conclusions:

  • Renal fibrosis is associated with PTEN downregulation.
  • DNMT3a negatively regulates PTEN, activating the PI3K/AKT pathway and promoting EMT, thus aggravating renal fibrosis.
Keywords:
DNMT3aPI3K/AKTPTENRenal fibrosisTGF-β1

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