ReviewNephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association2016
Regulation of the epithelial Na+ channel by the mTORC2/SGK1 pathway.
Review in Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
39 citing papers in PubMed, 54 citations in OpenAlex.
- Integrated mechanisms linking sodium-potassium imbalance to salt-sensitive hypertension.Physiological reports · 2025Review
- Review of mesenchymal stem cell-derived exosomes and their potential therapeutic roles in treating rheumatoid arthritis.Molecular biology reports · 2025Review
- Inhibition of mTORC2 promotes natriuresis in Dahl salt-sensitive rats via the decrease of NCC and ENaC activity.American journal of physiology. Renal physiology · 2024Article
- The mechanism of Shoutai Wan in the treatment of recurrent spontaneous abortion - A review.Heliyon · 2024Review
- Genetic imputation of kidney transcriptome, proteome and multi-omics illuminates new blood pressure and hypertension targets.Nature communications · 2024Article
- The role of serum-glucocorticoid regulated kinase 1 in reproductive viability: implications from prenatal programming and senescence.Molecular biology reports · 2024Review
- mTOR Regulates Mineralocorticoid Receptor Transcriptional Activity by ULK1-Dependent and -Independent Mechanisms.Endocrinology · 2024Article
- Vascular endothelial mineralocorticoid receptors and epithelial sodium channels in metabolic syndrome and related cardiovascular disease.Journal of molecular endocrinology · 2023Review
- Aldosterone: Renal Action and Physiological Effects.Comprehensive Physiology · 2023Article
- mTOR signaling in hair follicle and hair diseases: recent progress.Frontiers in medicine · 2023Review
- Look who's TORking: mTOR-mediated integration of cell status and external signals during limb development and endochondral bone growth.Frontiers in cell and developmental biology · 2023Review
- Kidney omics in hypertension: from statistical associations to biological mechanisms and clinical applications.Kidney international · 2022Review
- Regulation of distal tubule sodium transport: mechanisms and roles in homeostasis and pathophysiology.Pflugers Archiv : European journal of physiology · 2022Review
- Two adjacent phosphorylation sites in the C-terminus of the channel's α-subunit have opposing effects on epithelial sodium channel (ENaC) activity.Pflugers Archiv : European journal of physiology · 2022Article
- The effect of dexamethasone on uterine receptivity, mediated by the ERK1/2-mTOR pathway, and the implantation window: An experimental study.International journal of reproductive biomedicine · 2022Article
- Hydrogen peroxide (HScientific reports · 2021Article
- Selective Deletion of the Mechanistic Target of Rapamycin From the Renal Collecting Duct Principal Cell in Mice Down-Regulates the Epithelial Sodium Channel.Frontiers in physiology · 2021Article
- ENaC in Salt-Sensitive Hypertension: Kidney and Beyond.Current hypertension reports · 2020Review
- Role of the Ubiquitin Proteasome System in the Regulation of Blood Pressure: A Review.International journal of molecular sciences · 2020Review
- Role of Impaired Nutrient and Oxygen Deprivation Signaling and Deficient Autophagic Flux in Diabetic CKD Development: Implications for Understanding the Effects of Sodium-Glucose Cotransporter 2-Inhibitors.Journal of the American Society of Nephrology : JASN · 2020Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
2 authors at 2 institutions in 2 countries.
Funding
Abstract
The epithelial Na(+) channel (ENaC) is decisive for sodium reabsorption by the aldosterone-sensitive distal nephron (ASDN) of the kidney. ENaC is regulated by the serum- and glucocorticoid-inducible kinase 1 (SGK1), a kinase genomically upregulated by several hormones including glucocorticoids and mineralocorticoids. SGK1 is activated by the serine/threonine kinase mammalian target of rapamycin (mTOR) isoform mTORC2. SGK1 knockout (sgk1(-/-) mice) impairs renal Na(+) retention during salt depletion. The mTOR catalytic site inhibitor, PP242, but not mTORC1 inhibitor rapamycin, inhibits ENaC, decreases Na(+) flux in isolated perfused tubules and induces natriuresis in wild-type mice. PP242 does not lead to further impairment of Na(+) reabsorption in sgk1(-/-) mice. The mTORC2/SGK1 sensitive renal Na(+) retention leads to extracellular volume expansion with increase of blood pressure. A SGK1 gene variant (prevalence ∼ 3-5% in Caucasians, ∼ 10% in Africans) predisposes to hypertension, stroke, obesity and type 2 diabetes. Future studies will be required to define the role of mTORC2 in the regulation of further SGK1 sensitive transport proteins, such as further ion channels, carriers and the Na(+)/K(+)-ATPase. Moreover, studies are required disclosing the impact of mTORC2 on SGK1 sensitive disorders, such as hypertension, obesity, diabetes, thrombosis, stroke, inflammation, autoimmune disease, fibrosis and tumour growth.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.