ArticleAmerican journal of physiology. Renal physiology2015
The cpk model of recessive PKD shows glutamine dependence associated with the production of the oncometabolite 2-hydroxyglutarate.
Article in American journal of physiology. Renal physiology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
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Who cites it
33 citing papers in PubMed, 41 citations in OpenAlex.
- Plasma metabolites and lipids associate with kidney function and kidney volume in hypertensive ADPKD patients early in the disease course.BMC nephrology · 2019Trial
- Modeling Complex Developmental Disease: The Case of Polycystic Kidney Disease.Journal of developmental biology · 2026Review
- Wheat-Based Protein Slows Disease Progression in Pkd1 Knockout Mice.Function (Oxford, England) · 2025Article
- Physiologic mechanisms underlying polycystic kidney disease.Physiological reviews · 2025Review
- Metabolic reprogramming in polycystic kidney disease and other renal ciliopathies.EMBO molecular medicine · 2025Review
- A miRNA-Based Approach in Autosomal Dominant Polycystic Kidney Disease: Challenges and Insights from Adult to Pediatric Evidence.Molecular diagnosis & therapy · 2025Review
- Amino acid metabolism in kidney health and disease.Nature reviews. Nephrology · 2024Review
- A brief harvesting-freezing delay significantly alters the kidney metabolome and leads to false positive and negative results.American journal of physiology. Renal physiology · 2024Article
- Defects of renal tubular homeostasis and cystogenesis in theiScience · 2024Article
- ALTERATIONS IN HISTIDINE METABOLISM IS A FEATURE OF EARLY AUTOSOMAL DOMINANT POLYCYSTIC KIDNEY DISEASE (ADPKD).Transactions of the American Clinical and Climatological Association · 2024Article
- Cystin is required for maintaining fibrocystin (FPC) levels and safeguarding proteome integrity in mouse renal epithelial cells: A mechanistic connection between the kidney defects in cpk mice and human ARPKD.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2023Article
- Accelerated cystogenesis by dietary protein load is dependent on, but not initiated by kidney macrophages.Frontiers in medicine · 2023Article
- Identification of Serum Metabolites for Predicting Chronic Kidney Disease Progression according to Chronic Kidney Disease Cause.Metabolites · 2022Article
- Temporal Profile of Kynurenine Pathway Metabolites in a Rodent Model of Autosomal Recessive Polycystic Kidney Disease.International journal of tryptophan research : IJTR · 2022Article
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- Metabolic profiling in children and young adults with autosomal dominant polycystic kidney disease.Scientific reports · 2021Article
- Metabolic Reprogramming and Reconstruction: Integration of Experimental and Computational Studies to Set the Path Forward in ADPKD.Frontiers in medicine · 2021Review
- Is There a Functional Role of Mitochondrial Dysfunction in the Pathogenesis of ARPKD?Frontiers in medicine · 2021Article
- Metabolic Changes in Polycystic Kidney Disease as a Potential Target for Systemic Treatment.International journal of molecular sciences · 2020Review
- Super-enhancer-driven metabolic reprogramming promotes cystogenesis in autosomal dominant polycystic kidney disease.Nature metabolism · 2020Article
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Authors and funding
9 authors at 4 institutions in 1 country.
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Abstract
Since polycystic kidney disease (PKD) was first noted over 30 years ago to have neoplastic parallels, there has been a resurgent interest in elucidating neoplasia-relevant pathways in PKD. Taking a nontargeted metabolomics approach in the B6(Cg)-Cys1(cpk/)J (cpk) mouse model of recessive PKD, we have now characterized metabolic reprogramming in these tissues, leading to a glutamine-dependent TCA cycle shunt toward total 2-hydroxyglutarate (2-HG) production in cpk compared with B6 wild-type kidney tissue. After confirmation of increased 2-HG expression in immortalized collecting duct cpk cells as well as in human autosomal recessive PKD tissue using targeted analysis, we show that the increase in 2-HG is likely due to glutamine-sourced α-ketoglutarate. In addition, cpk cells require exogenous glutamine for growth such that inhibition of glutaminase-1 decreases cell viability as well as proliferation. This study is a demonstration of the striking parallels between recessive PKD and cancer metabolism. Our data, once confirmed in other PKD models, suggest that future therapeutic approaches targeting this pathway, such as using glutaminase inhibitors, have the potential to open novel treatment options for renal cystic disease.
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