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Hsp90 inhibition aggravates adriamycin-induced podocyte injury through intrinsic apoptosis pathway

Junyu Dong1, Zhihong Jiang1, Guorui Ma1

  • 1Department of Paediatrics, The First Affiliated Hospital of Henan University of Science & Technology, Luoyang, Henan, 471000, China.

Experimental Cell Research
|March 12, 2020
PubMed

Insights

Inhibition of heat shock protein 90 (Hsp90) worsens kidney podocyte injury and filtration barrier dysfunction in nephrotic syndrome (NS) models by enhancing apoptosis. Hsp90 inhibition may be a therapeutic target in NS.

Area of Science:

  • Nephrology
  • Molecular Biology
  • Cell Biology

Background:

  • Podocyte injury impairs kidney filtration, underlying idiopathic nephrotic syndrome (INS), common in children.
  • The role of heat shock protein 90 (Hsp90) in podocyte function and its association with NS remain unclear.

Purpose of the Study:

  • To investigate the role of Hsp90 in adriamycin (ADR)-induced podocyte injury and its potential link to NS pathogenesis.
  • To determine the mechanistic effects of Hsp90 inhibition on podocyte apoptosis and kidney filtration barrier function.

Main Methods:

  • Upregulation of Hsp90 was assessed in podocytes from ADR-induced nephropathy mice and ADR-treated cell lines.
  • The effects of Hsp90 inhibition using PU-H71 on podocyte apoptosis and filtration barrier function were evaluated.
  • The involvement of the intrinsic apoptotic pathway was examined using a pan-caspase inhibitor (zVAD-fmk).

Main Results:

  • Hsp90 was found to be upregulated in podocytes in ADR-induced nephropathy models.
  • Inhibition of Hsp90 with PU-H71 exacerbated ADR-induced podocyte apoptosis and filtration barrier impairment.
  • Hsp90 inhibition enhanced the intrinsic apoptotic pathway, and blocking apoptosis abrogated these effects.

Conclusions:

  • Hsp90 inhibition detrimentally impacts podocyte injury through the intrinsic apoptosis pathway.
  • Hsp90 plays a protective role in podocytes against ADR-induced injury.
  • Hsp90 inhibition represents a potential therapeutic target to avoid in NS therapy.

Keywords:
AdriamycinFiltration barrier functionHsp90Intrinsic apoptosis pathwayPU-H71Podocyte injury

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