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Published on: September 1, 2015
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.
Abstract:
Apoptosis in the cystic epithelium is observed in most rodent models of polycystic kidney disease (PKD) and in human autosomal dominant PKD (ADPKD). Apoptosis inhibition decreases cyst growth, whereas induction of apoptosis in the kidney of Bcl-2 deficient mice increases proliferation of the tubular epithelium and subsequent cyst formation. However, alternative evidence indicates that both induction of apoptosis as well as increased overall rates of apoptosis are associated with decreased cyst growth. Autophagic flux is suppressed in cell, zebra fish and mouse models of PKD and suppressed autophagy is known to be associated with increased apoptosis. There may be a link between apoptosis and autophagy in PKD. The mammalian target of rapamycin (mTOR), B-cell lymphoma 2 (Bcl-2) and caspase pathways that are known to be dysregulated in PKD, are also known to regulate both autophagy and apoptosis. Induction of autophagy in cell and zebrafish models of PKD results in suppression of apoptosis and reduced cyst growth supporting the hypothesis autophagy induction may have a therapeutic role in decreasing cyst growth, perhaps by decreasing apoptosis and proliferation in PKD. Future research is needed to evaluate the effects of direct autophagy inducers on apoptosis in rodent PKD models, as well as the cause and effect relationship between autophagy, apoptosis and cyst growth in PKD.
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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