Related Experiment Video

Updated: Jan 5, 2026

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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p66Shc regulates podocyte autophagy in high glucose environment through the Notch-PTEN-PI3K/Akt/mTOR pathway

Danna Zheng1,2,3,4, Mei Tao2,3,4, Xudong Liang2,3,4

  • 1Zhejiang Chinese Medical University, Zhejiang, PR China.

Histology and Histopathology
|October 26, 2019
PubMed
Abstract

Insights

p66Shc protein inhibits autophagy and promotes apoptosis in kidney podocytes, contributing to diabetic kidney disease (DKD). Targeting p66Shc may offer a new therapeutic strategy for DKD.

Area of Science:

  • Nephrology
  • Molecular Biology
  • Cell Biology

Background:

  • Diabetic kidney disease (DKD) involves podocyte injury, with autophagy playing a crucial role.
  • p66Shc is implicated in oxidative stress and apoptosis, and its expression is elevated in DKD podocytes.
  • The precise mechanism linking p66Shc to podocyte autophagy and injury in DKD is not fully understood.

Purpose of the Study:

  • To investigate the molecular function of p66Shc in podocytes under high glucose conditions.
  • To explore the potential of targeting p66Shc as a therapeutic strategy for DKD.

Main Methods:

  • Utilized a streptozotocin-induced mouse model of diabetes.
  • Assessed kidney injury using histological staining and electron microscopy.
  • Evaluated podocyte apoptosis and autophagy markers via TUNEL, Annexin V/PI, immunofluorescence, and western blotting.
  • Measured reactive oxygen species (ROS) levels using DHE/ET fluorescence.

Main Results:

  • Diabetic mice exhibited increased markers of kidney injury and p66Shc expression.
  • High glucose reduced podocyte viability; p66Shc overexpression exacerbated apoptosis.
  • p66Shc knockdown enhanced autophagy, while overexpression inhibited it by downregulating PTEN and upregulating mTOR signaling.
  • Inhibition of the Notch pathway with DAPT reduced p66Shc expression.

Conclusions:

  • p66Shc inhibits podocyte autophagy and induces apoptosis via the Notch-PTEN-PI3K/Akt/mTOR pathway in high glucose conditions.
  • These findings highlight p66Shc as a potential therapeutic target for DKD.

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