Study identifies myofibroblast autophagy as driver of cyst growth in polycystic kidney disease
Researchers found that autophagy—a cellular recycling process—in myofibroblasts drives cyst expansion in autosomal dominant polycystic kidney disease (ADPKD). The study used human tissue samples, cell cultures, and mouse models to show that blocking this autophagy reduced cyst growth and improved kidney function. The findings suggest targeting myofibroblast autophagy could be a new therapeutic approach for this progressive kidney disease.
A preprint study published on bioRxiv reveals that autophagy within myofibroblasts—cells that accumulate around kidney cysts—plays a critical role in promoting cyst expansion and fibrosis in ADPKD. Researchers examined autophagy markers in human ADPKD kidney tissue, cultured myofibroblasts, and a mouse model of the disease. When autophagy was inhibited either pharmacologically or through genetic deletion of the Atg5 gene in myofibroblasts, ADPKD mice showed significantly reduced cyst growth, decreased fibrosis, and improved kidney function, while control mice showed no adverse effects. The team identified a mechanism involving lactate produced by cyst epithelial cells, which stabilizes a protein called HIF1 in myofibroblasts and promotes autophagy. These findings suggest that targeting myofibroblast-specific autophagy or its upstream regulators could represent a new therapeutic strategy for limiting cyst growth and fibrosis in ADPKD.
What's missing
The study is a preprint and has not yet undergone peer review. The authors do not discuss potential limitations of translating these findings from mouse models to human patients, nor do they address the timeline for potential clinical translation of these findings into therapeutic interventions.
What different sources said
- bioRxivCenter
Myofibroblast- specific autophagy drives cyst growth in autosomal dominant polycystic kidney disease
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