ArticleJournal of the American Society of Nephrology : JASN2014
Activation of mTORC1 in collecting ducts causes hyperkalemia.
Article in Journal of the American Society of Nephrology : JASN, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 30 citations in OpenAlex.
- Klotho Deficiency Impairs Distal Potassium Homeostasis Through mTORC1-Dependent Suppression of ROMK.Acta physiologica (Oxford, England) · 2026Article
- Mechanistic Target of Rapamycin Complex 1 in Distal Convoluted Tubule and Renal Potassium Handling.Journal of the American Society of Nephrology : JASN · 2025Article
- Advances in Molecular Mechanisms of Kidney Disease: Integrating Renal Tumorigenesis of Hereditary Cancer Syndrome.International journal of molecular sciences · 2024Review
- HL156A, an AMP-Activated Protein Kinase Activator, Inhibits Cyst Growth in Autosomal Dominant Polycystic Kidney Disease.Biomolecules · 2024Article
- Proton pump inhibitors display anti-tumour potential in glioma.Cell proliferation · 2023Review
- Not all kidney cysts are created equal: a distinct renal cystogenic mechanism in tuberous sclerosis complex (TSC).Frontiers in physiology · 2023Review
- Hyperkalemia: Major but still understudied complication among heart transplant recipients.World journal of transplantation · 2021Review
- The long-term effects of rapamycin-based immunosuppressive protocols on the expression of renal aquaporins 1, 2, 3 and 4 water channels in rats.Histology and histopathology · 2021Article
- Kidney intercalated cells and the transcription factor FOXi1 drive cystogenesis in tuberous sclerosis complex.Proceedings of the National Academy of Sciences of the United States of America · 2021Article
- Rheb1 protects against cisplatin-induced tubular cell death and acute kidney injury via maintaining mitochondrial homeostasis.Cell death & disease · 2020Article
- Tuberous sclerosis complex exhibits a new renal cystogenic mechanism.Physiological reports · 2019Article
- Emodin mitigates podocytes apoptosis induced by endoplasmic reticulum stress through the inhibition of the PERK pathway in diabetic nephropathy.Drug design, development and therapy · 2018Article
- [Rictor/mTORC2 regulates blood-testis barrier and spermatogenesis in mice].Nan fang yi ke da xue xue bao = Journal of Southern Medical University · 2017Article
- mTORC1 regulates apoptosis and cell proliferation in pterygium via targeting autophagy and FGFR3.Scientific reports · 2017Article
- mTORC2 critically regulates renal potassium handling.The Journal of clinical investigation · 2016Article
- mTORC1 regulates PTHrP to coordinate chondrocyte growth, proliferation and differentiation.Nature communications · 2016Article
- mTORC1-mediated inhibition of polycystin-1 expression drives renal cyst formation in tuberous sclerosis complex.Nature communications · 2016Article
- Phosphorylation of ribosomal protein S6 mediates compensatory renal hypertrophy.Kidney international · 2015Article
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Authors and funding
15 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Mutation of TSC (encoding tuberous sclerosis complex protein) and activation of mammalian target of rapamycin (mTOR) have been implicated in the pathogenesis of several renal diseases, such as diabetic nephropathy and polycystic kidney disease. However, the role of mTOR in renal potassium excretion and hyperkalemia is not known. We showed that mice with collecting-duct (CD)-specific ablation of TSC1 (CDTsc1KO) had greater mTOR complex 1 (mTORC1) activation in the CD and demonstrated features of pseudohypoaldosteronism, including hyperkalemia, hyperaldosteronism, and metabolic acidosis. mTORC1 activation caused endoplasmic reticulum stress, columnar cell lesions, and dedifferentiation of CD cells with loss of aquaporin-2 and epithelial-mesenchymal transition-like phenotypes. Of note, mTORC1 activation also reduced the expression of serum- and glucocorticoid-inducible kinase 1, a crucial regulator of potassium homeostasis in the kidney, and decreased the expression and/or activity of epithelial sodium channel-α, renal outer medullary potassium channel, and Na(+), K(+)-ATPase in the CD, which probably contributed to the aldosterone resistance and hyperkalemia in these mice. Rapamycin restored these phenotypic changes. Overall, this study identifies a novel function of mTORC1 in regulating potassium homeostasis and demonstrates that loss of TSC1 and activation of mTORC1 results in dedifferentiation and dysfunction of the CD and causes hyperkalemia. The CDTsc1KO mice provide a novel model for hyperkalemia induced exclusively by dysfunction of the CD.
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