ArticleThe Journal of biological chemistry2012
Regulation of epithelial sodium channel trafficking by proprotein convertase subtilisin/kexin type 9 (PCSK9).
Article in The Journal of biological chemistry, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers, 3 of them syntheses that pooled it.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
40 citing papers in PubMed, 3 syntheses or guidelines pooled it, 91 citations in OpenAlex.
- Association Between Circulating Proprotein Convertase Subtilisin/Kexin Type 9 and Major Adverse Cardiovascular Events, Stroke, and All-Cause Mortality: Systemic Review and Meta-Analysis.Frontiers in cardiovascular medicine · 2021Pooled it
- Pooled it
- The Role of Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9) in Cardiovascular Homeostasis: A Non-Systematic Literature Review.Current cardiology reviews · 2017Pooled it
- PCSK9 in critical illness - It's not all about lipids.Annals of clinical biochemistry · 2026Review
- Depletion of renal cortical collecting duct-secreted PCSK9 in early proteinuria prevents sustained nephrotic syndrome-related hypercholesterolemia.American journal of physiology. Renal physiology · 2026Article
- Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9) in Alzheimer's Disease: Recent Advances and Controversies.Molecular neurobiology · 2025Review
- The function of PCSK9 in doxorubicin-induced cardiotoxicity and its underlying mechanism.Scientific reports · 2025Article
- Emerging roles of PCSK9 in kidney disease: lipid metabolism, megalin regulation and proteinuria.Pflugers Archiv : European journal of physiology · 2025Review
- PCSK9 in Vascular Aging and Age-Related Diseases.Aging and disease · 2025Review
- Targeting proprotein convertase subtilisin/kexin type 9 (PCSK9): from bench to bedside.Signal transduction and targeted therapy · 2024Review
- Proprotein convertase subtilisin/kexin type 9 deficiency in extrahepatic tissues: emerging considerations.Frontiers in pharmacology · 2024Review
- Increased serum PCSK9 levels are associated with renal function impairment in patients with type 2 diabetes mellitus.Renal failure · 2023Article
- PCSK9 and Other Metabolic Targets to Counteract Ischemia/Reperfusion Injury in Acute Myocardial Infarction and Visceral Vascular Surgery.Journal of clinical medicine · 2022Review
- Insight into the Evolving Role of PCSK9.Metabolites · 2022Review
- Nephrotic Syndrome Complications - New and Old. Part 1.Maedica · 2022Article
- Evaluation of cardiovascular events and progression to end-stage renal disease in patients with dyslipidemia and chronic kidney disease from the North-Eastern area of Romania.International urology and nephrology · 2022Article
- The Emerging Roles of Intracellular PCSK9 and Their Implications in Endoplasmic Reticulum Stress and Metabolic Diseases.Metabolites · 2022Review
- PCSK9Qβ-003 Vaccine Attenuates Atherosclerosis in Apolipoprotein E-Deficient Mice.Cardiovascular drugs and therapy · 2021Article
- Association Between Genetically Proxied Lipid-Lowering Drug Targets and Renal Cell Carcinoma: A Mendelian Randomization Study.Frontiers in nutrition · 2021Article
- The systemic implication of novel non-statin therapies in cardiovascular diabetology: PCSK9 as a case model.Cardiovascular endocrinology & metabolism · 2020Review
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
The epithelial Na(+) channel (ENaC) is critical for Na(+) homeostasis and blood pressure control. Defects in its regulation cause inherited forms of hypertension and hypotension. Previous work found that ENaC gating is regulated by proteases through cleavage of the extracellular domains of the α and γ subunits. Here we tested the hypothesis that ENaC is regulated by proprotein convertase subtilisin/kexin type 9 (PCSK9), a protease that modulates the risk of cardiovascular disease. PCSK9 reduced ENaC current in Xenopus oocytes and in epithelia. This occurred through a decrease in ENaC protein at the cell surface and in the total cellular pool, an effect that did not require the catalytic activity of PCSK9. PCSK9 interacted with all three ENaC subunits and decreased their trafficking to the cell surface by increasing proteasomal degradation. In contrast to its previously reported effects on the LDL receptor, PCSK9 did not alter ENaC endocytosis or degradation of the pool of ENaC at the cell surface. These results support a role for PCSK9 in the regulation of ENaC trafficking in the biosynthetic pathway, likely by increasing endoplasmic reticulum-associated degradation. By reducing ENaC channel number, PCSK9 could modulate epithelial Na(+) absorption, a major contributor to blood pressure control.
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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.