Apoptosis and autophagy in polycystic kidney disease (PKD)

Kristen L Nowak1, Charles L Edelstein1

  • 1Division of Renal Diseases and Hypertension, Univ. of Colorado Anschutz Medical Campus, Aurora, CO, USA.

Cellular Signalling
|December 28, 2019
PubMed

Insights

In polycystic kidney disease (PKD), apoptosis and autophagy are linked. Inducing autophagy may reduce cyst growth by suppressing apoptosis and proliferation, suggesting a potential therapeutic strategy for PKD.

Area of Science:

  • Nephrology
  • Cell Biology
  • Molecular Medicine

Background:

  • Apoptosis is observed in cystic epithelia in polycystic kidney disease (PKD) models and human autosomal dominant PKD (ADPKD).
  • Evidence on apoptosis's role in PKD is conflicting: inhibition can decrease cyst growth, but induction sometimes increases it.
  • Autophagic flux is suppressed in PKD models, and this suppression is linked to increased apoptosis.

Purpose of the Study:

  • To explore the relationship between apoptosis and autophagy in PKD.
  • To investigate the potential therapeutic role of autophagy induction in managing PKD cyst growth.

Main Methods:

  • Review of existing literature on apoptosis and autophagy pathways in PKD.
  • Analysis of signaling pathways like mTOR, Bcl-2, and caspases, known to be dysregulated in PKD and involved in apoptosis/autophagy regulation.

Main Results:

  • Suppressed autophagy in PKD models correlates with increased apoptosis.
  • Induction of autophagy in cell and zebrafish PKD models suppressed apoptosis and reduced cyst growth.
  • Dysregulation of mTOR, Bcl-2, and caspase pathways impacts both apoptosis and autophagy in PKD.

Conclusions:

  • Autophagy induction shows promise as a therapeutic strategy for PKD, potentially by reducing apoptosis and cell proliferation.
  • Further research is required to validate autophagy inducers in rodent PKD models and clarify the interplay between autophagy, apoptosis, and cystogenesis.

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