Activation of necroptosis pathway in podocyte contributes to the pathogenesis of focal segmental glomerular sclerosis

Related Experiment Video

Updated: Sep 2, 2025

Mechanism of Kemeng Fang's Inhibition of Podocyte Apoptosis in Rats with Membranous Nephropathy through the PI3K/AKT Signaling Pathway
07:15

Mechanism of Kemeng Fang's Inhibition of Podocyte Apoptosis in Rats with Membranous Nephropathy through the PI3K/AKT Signaling Pathway

Published on: August 23, 2024

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Haoqiang Hu1,2, Mengyuan Li2, Binfeng Chen2

  • 1Department of Nephrology, Affiliated Dongguan People's Hospital, Southern Medical University (Dongguan People's Hospital), Dongguan, 523000, China.

Clinical and Experimental Nephrology
|August 4, 2022
PubMed
Abstract

Insights

Necroptosis, a programmed cell death pathway, is activated in focal segmental glomerulosclerosis (FSGS). Inhibiting necroptosis reduced kidney damage and proteinuria in a mouse model, suggesting it as a potential therapeutic target for FSGS.

Area of Science:

  • Nephrology
  • Cell Biology
  • Molecular Medicine

Background:

  • Focal segmental glomerulosclerosis (FSGS) is characterized by podocyte injury and proteinuria, with unclear underlying mechanisms.
  • Necroptosis, a form of programmed cell death involving RIP3 and MLKL, is a significant cell death pathway not previously studied in FSGS.

Purpose of the Study:

  • To investigate the role of necroptosis in FSGS pathogenesis.
  • To explore necroptosis as a potential therapeutic target for FSGS.

Main Methods:

  • Analysis of public GEO data and cultured human podocytes stimulated with adriamycin (ADR).
  • Examination of necroptosis markers (p-RIP3, p-MLKL) in FSGS patients and ADR-induced nephropathy mice.
  • Assessment of necroptosis inhibition using GSK872 in vitro and in vivo.

Main Results:

  • ADR-injured podocytes showed upregulated necroptosis and NLRP3 inflammasome pathways.
  • Active necroptosis markers (p-RIP3, p-MLKL) were elevated in FSGS patients and ADR-induced mice.
  • GSK872 treatment reduced necroptosis, NLRP3 activation, and attenuated proteinuria and kidney lesions in mice.

Conclusions:

  • The necroptosis pathway is implicated in FSGS development.
  • Inhibition of necroptosis shows promise in ameliorating FSGS.
  • Targeting necroptosis may offer a novel therapeutic strategy for FSGS.
Keywords:
Focal segmental glomerular sclerosisInflammasomeNecroptosisPodocyte

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