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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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mPGES-1-derived prostaglandin E2 stimulates Stat3 to promote podocyte apoptosis

Jing Yu1,2,3, Yimei Wu1,2,3, Lu Wang1,2,3

  • 1Department of Nephrology, Children's Hospital of Nanjing Medical University, Nanjing, 210008, People's Republic of China.

Apoptosis : an International Journal on Programmed Cell Death
|September 8, 2017
PubMed

Insights

Microsomal prostaglandin E synthase-1 (mPGES-1) derived PGE2 activates Stat3 signaling, promoting podocyte apoptosis. Targeting this mPGES-1/PGE2/Stat3 pathway may treat podocytopathy.

Area of Science:

  • Nephrology
  • Molecular Biology
  • Biochemistry

Background:

  • Microsomal prostaglandin E synthase-1 (mPGES-1) is implicated in adriamycin (Adr)-induced podocyte apoptosis.
  • The precise molecular mechanisms underlying mPGES-1's role in podocyte injury remain incompletely understood.

Purpose of the Study:

  • To investigate the role of the mPGES-1/PGE2 cascade in activating Stat3 signaling.
  • To determine the contribution of Stat3 to PGE2- and Adr-induced podocyte apoptosis.

Main Methods:

  • Murine podocytes were treated with PGE2 and Adr.
  • Key molecular pathways, including Stat3 phosphorylation and mPGES-1 expression, were analyzed.
  • Specific inhibitors (S3I-201) and silencing (siRNA) were employed to block target pathways.

Main Results:

  • PGE2 treatment dose- and time-dependently increased Stat3 phosphorylation, podocyte apoptosis, and inflammatory cytokine production (IL-6, IL-17, MCP-1, ICAM-1), while reducing podocin.
  • Stat3 inhibition ameliorated PGE2- and Adr-induced podocyte apoptosis and podocin reduction.
  • Silencing mPGES-1 inhibited Adr-induced Stat3 phosphorylation, PGE2 production, and inflammatory cytokine release.

Conclusions:

  • The mPGES-1-derived PGE2 cascade activates Stat3 signaling, contributing to podocyte apoptosis.
  • Targeting the mPGES-1/PGE2/Stat3 signaling pathway presents a potential therapeutic strategy for podocytopathies.
Keywords:
AdriamycinPGE2Podocyte apoptosisStat3mPGES-1

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