ArticleJournal of the American Society of Nephrology : JASN2015
The epithelial sodium channel γ-subunit is processed proteolytically in human kidney.
Article in Journal of the American Society of Nephrology : JASN, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT02823613 (The Influence of High and Low Salt on Exosomes in the Urine), which is not on this map. Cited by 33 papers.
What it found
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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.
The Influence of High and Low Salt on Exosomes in the Urine
Who cites it
33 citing papers in PubMed, 61 citations in OpenAlex.
- Albuminuria is associated with an increased prostasin in urine while aldosterone has no direct effect on urine and kidney tissue abundance of prostasin.Pflugers Archiv : European journal of physiology · 2017Trial
- Resistance to doxorubicin-induced proteinuria and proteolytic activation of ENaC in 129S2/SvPas mice.Physiological reports · 2025Article
- Urinary Plasminogen as a Marker of Disease Progression in Human Glomerular Disease.American journal of kidney diseases : the official journal of the National Kidney Foundation · 2024Article
- Influence of proteolytic cleavage of ENaC's γ subunit upon NaAmerican journal of physiology. Renal physiology · 2024Article
- Nephrotic Syndrome: From Pathophysiology to Novel Therapeutic Approaches.Biomedicines · 2024Review
- Activation of renal epithelial NaFrontiers in pediatrics · 2024Article
- Proteolytic Activation of the Epithelial Sodium Channel (ENaC): Its Mechanisms and Implications.International journal of molecular sciences · 2023Review
- Mice lacking γENaC palmitoylation sites maintain benzamil-sensitive Na+ transport despite reduced channel activity.JCI insight · 2023Article
- Aldosterone: Renal Action and Physiological Effects.Comprehensive Physiology · 2023Article
- Role of ion channels in the mechanism of proteinuria (Review).Experimental and therapeutic medicine · 2023Review
- Kidney-Specific CAP1/Prss8-Deficient Mice Maintain ENaC-Mediated Sodium Balance through an Aldosterone Independent Pathway.International journal of molecular sciences · 2022Article
- Sodium retention in the nephrotic syndrome and the non-enzymatic function of prostasin.Pflugers Archiv : European journal of physiology · 2022Article
- Proteinuria is accompanied by intratubular complement activation and apical membrane deposition of C3dg and C5b-9 in kidney transplant recipients.American journal of physiology. Renal physiology · 2022Observational
- The Effect of Dynasore Upon the Negative Interaction Between ENaC and CFTR Channels in Xenopus laevis Oocytes.The Journal of membrane biology · 2022Article
- Aldosterone-Regulated Sodium Transport and Blood Pressure.Frontiers in physiology · 2022Review
- Proteolysis and inflammation of the kidney glomerulus.Cell and tissue research · 2021Review
- Regulating ENaC's gate.American journal of physiology. Cell physiology · 2020Review
- The epithelial NaPflugers Archiv : European journal of physiology · 2019Article
- Is urinary excretion of plasminogen associated with development of pre-eclampsia? An observational, explorative case-control study.BMJ open · 2019Observational
- A bacterial display system for effective selection of protein-biotin ligase BirA variants with novel peptide specificity.Scientific reports · 2019Article
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The epithelial sodium channel (ENaC) of the kidney is necessary for extracellular volume homeostasis and normal arterial BP. Activity of ENaC is enhanced by proteolytic cleavage of the γ-subunit and putative release of a 43-amino acid inhibitory tract from the γ-subunit ectodomain. We hypothesized that proteolytic processing of γENaC occurs in the human kidney under physiologic conditions and that proteinuria contributes to aberrant proteolytic activation. Here, we used monoclonal antibodies (mAbs) with specificity to the human 43-mer inhibitory tract (N and C termini, mAbinhibit, and mAb4C11) and the neoepitope generated after proteolytic cleavage at the prostasin/kallikrein cleavage site (K181-V182 and mAbprostasin) to examine human nephrectomy specimens. By immunoblotting, kidney cortex homogenate from patients treated with angiotensin II type 1 receptor antagonists (n=6) or angiotensin-converting enzyme inhibitors (n=6) exhibited no significant difference in the amount of full-length or furin-cleaved γENaC or the furin-cleaved-to-full-length ratio of γENaC compared with homogenate from patients on no medication (n=5). Patients treated with diuretics (n=4) displayed higher abundance of full-length and furin-cleaved γENaC, with no significant change in the furin-cleaved-to-full-length γENaC ratio. In patients with proteinuria (n=6), the inhibitory tract was detected only in full-length γENaC by mAbinhibit. Prostasin/kallikrein-cleaved γENaC was detected consistently only in tissue from patients with proteinuria and observed in collecting ducts. In conclusion, human kidney γENaC is subject to proteolytic cleavage, yielding fragments compatible with furin cleavage, and proteinuria is associated with cleavage at the putative prostasin/kallikrein site and removal of the inhibitory tract within γENaC.
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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.