ArticleNephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association2015
An mTOR kinase inhibitor slows disease progression in a rat model of polycystic kidney disease.
Article in Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 42 citations in OpenAlex.
- mTOR promotes the formation and growth of tertiary lymphoid tissues in the kidney.Frontiers in immunology · 2025Article
- Raising serum uric acid with a uricase inhibitor worsens PKD in rat and mouse models.American journal of physiology. Renal physiology · 2024Article
- Sodium-glucose cotransporter inhibition in polycystic kidney disease: fact or fiction.Clinical kidney journal · 2022Review
- Renal plasticity revealed through reversal of polycystic kidney disease in mice.Nature genetics · 2021Article
- Nephronophthisis-Pathobiology and Molecular Pathogenesis of a Rare Kidney Genetic Disease.Genes · 2021Review
- Autophagy induction promotes renal cyst growth in polycystic kidney disease.EBioMedicine · 2020Article
- Transgenic expression of Sag/Rbx2 E3 causes early stage tumor promotion, late stage cytogenesis and acinar loss in the Kras-PDAC model.Neoplasia (New York, N.Y.) · 2020Article
- Apoptosis and autophagy in polycystic kidney disease (PKD).Cellular signalling · 2020Review
- Inactivation ofAmerican journal of physiology. Renal physiology · 2019Article
- A study of sirolimus and mTOR kinase inhibitor in a hypomorphicAmerican journal of physiology. Renal physiology · 2019Article
- Transplant immunosuppressive drugs in urology.Translational andrology and urology · 2019Review
- The Role of Primary Cilia in the Crosstalk between the Ubiquitin⁻Proteasome System and Autophagy.Cells · 2019Review
- Emerging targeted strategies for the treatment of autosomal dominant polycystic kidney disease.Clinical kidney journal · 2018Review
- Canonical Wnt inhibitors ameliorate cystogenesis in a mouse ortholog of human ADPKD.JCI insight · 2018Article
- Ryanodine Receptors in Autophagy: Implications for Neurodegenerative Diseases?Frontiers in cellular neuroscience · 2018Review
- Therapeutic Use of mTOR Inhibitors in Renal Diseases: Advances, Drawbacks, and Challenges.Oxidative medicine and cellular longevity · 2018Review
- Rapamycin treatment dose-dependently improves the cystic kidney in a new ADPKD mouse model via the mTORC1 and cell-cycle-associated CDK1/cyclin axis.Journal of cellular and molecular medicine · 2017Article
- Variable Cyst Development in Autosomal Dominant Polycystic Kidney Disease: The Biologic Context.Journal of the American Society of Nephrology : JASN · 2016Review
- Nephronophthisis: should we target cysts or fibrosis?Pediatric nephrology (Berlin, Germany) · 2016Review
- Regulation of the epithelial Na+ channel by the mTORC2/SGK1 pathway.Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association · 2016Review
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
backgroundThe mTOR pathway, which consists of mTOR complex 1 (mTORC1) and mTOR complex 2 (mTORC2), is activated in polycystic kidney disease (PKD) kidneys. Sirolimus and everolimus indirectly bind and inhibit mTORC1. A novel group of drugs, the mTOR kinase inhibitors, directly bind to mTOR kinase, thus inhibiting both mTORC1 and 2. The aim of the study was to determine the therapeutic effect of an mTOR kinase inhibitor, PP242, in the Han:SPRD rat (Cy/+) model of PKD.
methodsMale rats were treated with PP242 5 mg/kg/day IP or vehicle for 5 weeks.
resultsPP242 significantly reduced the kidney enlargement, the cyst density and the blood urea nitrogen in Cy/+ rats. On immunoblot of kidneys, PP242 resulted in a decrease in pS6, a marker of mTORC1 signaling and pAkt(Ser473), a marker of mTORC2 signaling. mTORC plays an important role in regulating cytokine production. There was an increase in IL-1, IL-6, CXCL1 and TNF-α in Cy/+ rat kidneys that was unaffected by PP242. Apoptosis or proliferation is known to play a causal role in cyst growth. PP242 had no effect on caspase-3 activity, TUNEL positive or active caspase-3-positive tubular cells in Cy/+ kidneys. PP242 reduced the number of proliferating cells per cyst and per non-cystic tubule in Cy/+ rats.
conclusionsIn a rat model of autosomal dominant polycystic kidney disease, PP242 treatment (i) decreases proliferation in cystic and non-cystic tubules; (ii) inhibits renal enlargement and cystogenesis and (iii) significantly reduces the loss of kidney function.
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