ArticleJournal of the American Society of Nephrology : JASN2014
Alterations in the ubiquitin proteasome system in persistent but not reversible proteinuric diseases.
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 20 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
20 citing papers in PubMed, 44 citations in OpenAlex.
- Programmed Cell Death: A Key Mechanism of Traditional Chinese Medicine in the Treatment of Membranous Nephropathy.Drug design, development and therapy · 2026Review
- Lysosome stress response and mitochondria injury are the earliest detectable alteration in FSGS.Scientific reports · 2025Article
- Identification of conserved gene expression changes across common glomerular diseases by spatial transcriptomics.Journal of nephrology · 2025Article
- The Life of a Kidney Podocyte.Acta physiologica (Oxford, England) · 2025Review
- Pathogenesis of Focal Segmental Glomerulosclerosis and Minimal Change Disease: Insights from Glomerular Proteomics.Life (Basel, Switzerland) · 2025Article
- RBBP6-Mediated ERRα Degradation Contributes to Mitochondrial Injury in Renal Tubular Cells in Diabetic Kidney Disease.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- CCDC92 promotes podocyte injury by regulating PA28α/ABCA1/cholesterol efflux axis in type 2 diabetic mice.Acta pharmacologica Sinica · 2024Article
- The proteasome modulates endocytosis specifically in glomerular cells to promote kidney filtration.Nature communications · 2024Article
- Nutrition for Podocyte Repair in Nephrotic Syndrome?Nutrients · 2023Article
- Non-functional ubiquitin C-terminal hydrolase L1 drives podocyte injury through impairing proteasomes in autoimmune glomerulonephritis.Nature communications · 2023Article
- Cytoskeletal protein degradation in brain death donor kidneys associates with adverse posttransplant outcomes.American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons · 2022Article
- Urinary Protein and Peptide Markers in Chronic Kidney Disease.International journal of molecular sciences · 2021Review
- Deconvolution of Focal Segmental Glomerulosclerosis Pathophysiology Using Transcriptomics Techniques.Glomerular diseases · 2021Review
- Lysosome function in glomerular health and disease.Cell and tissue research · 2021Review
- Association ofJournal of personalized medicine · 2020Article
- Role of A20/TNFAIP3 deficiency in lupus nephritis in MRL/lpr mice.Clinical and experimental nephrology · 2020Article
- The ubiquitin-proteasome system in kidney physiology and disease.Nature reviews. Nephrology · 2019Review
- Article
- Membranous Nephropathy and Anti-Podocytes Antibodies: Implications for the Diagnostic Workup and Disease Management.BioMed research international · 2018Review
- Podocyte-actin dynamics in health and disease.Nature reviews. Nephrology · 2016Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
19 authors at 5 institutions in 3 countries.
Funding
Abstract
Podocytes are the key cells affected in nephrotic glomerular kidney diseases, and they respond uniformly to injury with cytoskeletal rearrangement. In nephrotic diseases, such as membranous nephropathy and FSGS, persistent injury often leads to irreversible structural damage, whereas in minimal change disease, structural alterations are mostly transient. The factors leading to persistent podocyte injury are currently unknown. Proteolysis is an irreversible process and could trigger persistent podocyte injury through degradation of podocyte-specific proteins. We, therefore, analyzed the expression and functional consequence of the two most prominent proteolytic systems, the ubiquitin proteasome system (UPS) and the autophagosomal/lysosomal system, in persistent and transient podocyte injuries. We show that differential upregulation of both proteolytic systems occurs in persistent human and rodent podocyte injury. The expression of specific UPS proteins in podocytes differentiated children with minimal change disease from children with FSGS and correlated with poor clinical outcome. Degradation of the podocyte-specific protein α-actinin-4 by the UPS depended on oxidative modification in membranous nephropathy. Notably, the UPS was overwhelmed in podocytes during experimental glomerular disease, resulting in abnormal protein accumulation and compensatory upregulation of the autophagosomal/lysosomal system. Accordingly, inhibition of both proteolytic systems enhanced proteinuria in persistent nephrotic disease. This study identifies altered proteolysis as a feature of persistent podocyte injury. In the future, specific UPS proteins may serve as new biomarkers or therapeutic targets in persistent nephrotic syndrome.
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.