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[Regulation of heat shock protein 27/activating transcription factor-5 complex and its implication in podocyte

Li-zhu Wang1, Qiang Huang, Hai-chang Huang

  • 1Division of Nephrology, First Hospital & Institute of Nephrology, Peking University, Beijing 100034, China.

Zhonghua Yi Xue Za Zhi
|May 9, 2006
PubMed
Abstract

Insights

High glucose increases podocyte apoptosis by forming a heat shock protein (HSP)27/activating transcription factor (ATF)-5 complex via the ERK pathway. This complex plays a role in high glucose-induced podocyte injury.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Nephrology

Background:

  • Diabetic nephropathy is a leading cause of kidney failure.
  • Podocyte injury is a key event in the progression of diabetic nephropathy.
  • Heat shock proteins (HSP) and transcription factors are implicated in cellular stress responses.

Purpose of the Study:

  • To investigate the regulation of the heat shock protein (HSP)27/activating transcription factor (ATF)-5 complex in podocytes under high glucose conditions.
  • To elucidate the underlying mechanisms, including the involvement of extracellular signal-regulated kinase (ERK) and p38 signaling pathways.
  • To determine the role of the HSP27/ATF5 complex in high glucose-induced podocyte apoptosis.

Main Methods:

  • Primary mouse kidney podocytes were cultured under normal (5.5 mmol/L D-glucose) and high glucose (30 mmol/L D-glucose) conditions.
  • Cell apoptosis was assessed using Hoechst 33342 staining, fluorescence microscopy, and flow cytometry.
  • Western blotting was employed to analyze ERK and p38 signaling pathway activation.
  • Co-immunoprecipitation was used to detect the HSP27/ATF5 complex formation.
  • Specific pathway inhibitors (PD98059 for ERK, SB203580 for p38) were used to investigate their roles.

Main Results:

  • High glucose significantly increased podocyte apoptosis compared to normal glucose.
  • The HSP27/ATF5 complex was detected in podocytes, and its level was significantly elevated under high glucose conditions.
  • Both ERK and p38 signaling pathways were activated by high glucose.
  • Inhibition of the ERK pathway (PD98059) reduced HSP27/ATF5 complex formation and exacerbated podocyte apoptosis.
  • Inhibition of the p38 pathway (SB203580) did not significantly affect HSP27/ATF5 complex levels but reduced podocyte apoptosis.

Conclusions:

  • High glucose induces the formation of the HSP27/ATF5 complex in podocytes primarily through the ERK signaling pathway.
  • The HSP27/ATF5 complex appears to play a regulatory role in high glucose-induced podocyte apoptosis.
  • Targeting the ERK/HSP27/ATF5 pathway may offer a therapeutic strategy for diabetic nephropathy.

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