ArticleAmerican journal of physiology. Renal physiology2011
mTORC1/2 and rapamycin in female Han:SPRD rats with polycystic kidney disease.
Article in American journal of physiology. Renal physiology, 2011. 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, 44 citations in OpenAlex.
- Treatment of geographic atrophy with subconjunctival sirolimus: results of a phase I/II clinical trial.Investigative ophthalmology & visual science · 2013Trial
- Physiologic mechanisms underlying polycystic kidney disease.Physiological reviews · 2025Review
- mTOR promotes the formation and growth of tertiary lymphoid tissues in the kidney.Frontiers in immunology · 2025Article
- Progress on the mechanism of Polycystin-1 in bone remodeling.Frontiers in cell and developmental biology · 2025Review
- Folate conjugated nanomedicines for selective inhibition of mTOR signaling in polycystic kidneys at clinically relevant doses.Biomaterials · 2023Article
- Sodium-glucose cotransporter inhibition in polycystic kidney disease: fact or fiction.Clinical kidney journal · 2022Review
- Single Gene Mutations inBiology · 2022Article
- New Insights into the Mechanisms of Chaperon-Mediated Autophagy and Implications for Kidney Diseases.Cells · 2022Review
- AMPK and Polycystic Kidney Disease Drug Development: An Interesting Off-Target Target.Frontiers in medicine · 2022Review
- Autophagy in major human diseases.The EMBO journal · 2021Review
- A study of sirolimus and mTOR kinase inhibitor in a hypomorphicAmerican journal of physiology. Renal physiology · 2019Article
- Metabolism and mitochondria in polycystic kidney disease research and therapy.Nature reviews. Nephrology · 2018Review
- Dual mTOR/PI3K inhibition limits PI3K-dependent pathways activated upon mTOR inhibition in autosomal dominant polycystic kidney disease.Scientific reports · 2018Article
- Canonical Wnt inhibitors ameliorate cystogenesis in a mouse ortholog of human ADPKD.JCI insight · 2018Article
- Inhibition of Mammalian Target of Rapamycin Complex 1 Attenuates Salt-Induced Hypertension and Kidney Injury in Dahl Salt-Sensitive Rats.Hypertension (Dallas, Tex. : 1979) · 2017Article
- 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
- Roles of mTOR complexes in the kidney: implications for renal disease and transplantation.Nature reviews. Nephrology · 2016Review
- Scattered Deletion of PKD1 in Kidneys Causes a Cystic Snowball Effect and Recapitulates Polycystic Kidney Disease.Journal of the American Society of Nephrology : JASN · 2015Article
- An mTOR kinase inhibitor slows disease progression in a rat model of polycystic kidney disease.Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association · 2015Article
- An mTOR anti-sense oligonucleotide decreases polycystic kidney disease in mice with a targeted mutation in Pkd2.Human molecular genetics · 2014Article
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
Rapamycin slows disease progression in the male Han:SPRD (Cy/+) rat with polycystic kidney disease (PKD). The aim of this study was to determine the effect of rapamycin on PKD and the relative contributions of the proproliferative mammalian target of rapamycin complexes 1 and 2 (mTORC1 and mTORC2) in female Cy/+ rats. Female Cy/+ rats were treated with rapamycin from 4 to 12 wk of age. In vehicle-treated Cy/+ rats, kidney volume increased by 40% and cyst volume density (CVD) was 19%. Phosphorylated S6 (p-S6) ribosomal protein, a marker of mTORC1 activity, was increased in Cy/+ rats compared with normal littermate controls (+/+) and decreased by rapamycin. Despite activation of mTORC1 in female Cy/+ rats, rapamycin had no effect on kidney size, CVD, number of PCNA-positive cystic tubular cells, caspase-3 activity, or the number of terminal deoxynucleotidyl transferase dUTP-mediated nick-end label-positive apoptotic cells. To determine a reason for the lack of effect of rapamycin, we studied the mTORC2 signaling pathway. On immunoblot of kidney, phosphorylated (Ser473) Akt (p-Akt), a marker of mTORC2 activity, was increased in female Cy/+ rats treated with rapamycin. Phosphorylated (Ser657) PKCα, a substrate of mTORC2, was unaffected by rapamycin in females. In contrast, in male rats, where rapamycin significantly decreases PKD, p-Akt (Ser473) was decreased by rapamcyin. PKCα (Ser657) was increased in male Cy/+ rats but was unaffected by rapamycin. In summary, in female Cy/+ rats, rapamycin had no effect on PKD and proproliferative p-Akt (Ser473) activity was increased by rapamycin. There were differential effects of rapamycin on mTORC2 signaling in female vs. male Cy/+ rats.
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