ArticleNature communications2016
Endoplasmic reticulum stress drives proteinuria-induced kidney lesions via Lipocalin 2.
Article in Nature communications, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 69 papers, 2 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
69 citing papers in PubMed, 2 syntheses or guidelines pooled it, 118 citations in OpenAlex.
- Dent disease: clinical practice recommendations.Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association · 2025Guideline
- Are Urinary Tubular Injury Markers Useful in Chronic Kidney Disease? A Systematic Review and Meta Analysis.PloS one · 2016Pooled it
- LCN2 Associated With the Bidirectional Cardio-Kidney Link in Patients With Type 2 Diabetes and Cardiovascular-Kidney-Metabolic Syndrome.Medical science monitor : international medical journal of experimental and clinical research · 2026Article
- Lipocalin-2 Is Induced by Uromodulin Aggregates without Affecting Kidney Disease Progression in Autosomal Dominant Tubulointerstitial Kidney Disease- UMOD.Journal of the American Society of Nephrology : JASN · 2026Article
- Endoplasmic Reticulum Stress in the Keratinocytes Contributes to Chronic Itch by Activation of Lipocalin 2/MC4R/TRPV1 Pathway.Neuroscience bulletin · 2026Article
- Article
- Small molecules targeting regulated cell death for chronic kidney disease therapy.Journal of pharmaceutical analysis · 2026Review
- Article
- Oxidative stress and endoplasmic reticulum stress in acute kidney injury: mechanistic crosstalk and therapeutic modulation.Frontiers in medicine · 2026Review
- Adipokines and Vascular Modulators in CKM: Emerging Biomarkers as Diagnostic and Therapeutic Targets.International journal of molecular sciences · 2025Review
- Urinary NGAL as an Early Marker of Renal Dysfunction in Dogs with Heartworm Disease and Pulmonary Hypertension.Animals : an open access journal from MDPI · 2025Article
- Endoplasmic Reticulum Stress Drives Neuroinflammation Through Lipocalin 2 Upregulation in Retinal Microglia After Optic Nerve Injury.Investigative ophthalmology & visual science · 2025Article
- Oncogenic and tumor-suppressive roles of Lipocalin 2 (LCN2) in tumor progression.Oncology research · 2025Review
- Broad-spectrum therapeutic potential of 4-phenylbutyrate in neurological and systemic diseases of viral and non-viral origin.Frontiers in pharmacology · 2025Review
- TGFB1/CXCL5 axis regulation by LCN2 overexpression: a promising strategy to inhibit colorectal cancer metastasis and enhance prognosis.Frontiers in immunology · 2025Article
- Development of Predictive Models for Progression from Diabetic Kidney Disease to End-Stage Renal Disease in Type 2 Diabetes Mellitus: A Retrospective Cohort Study.Diabetes, metabolic syndrome and obesity : targets and therapy · 2025Article
- Impaired Glucose Metabolism, Primary Cilium Defects, and Kidney Cystogenesis in Glycogen Storage Disease Type Ia.Journal of the American Society of Nephrology : JASN · 2024Article
- Review
- The role of the C5a-C5aR pathway in iron metabolism and gastric cancer progression.Frontiers in immunology · 2024Article
- Tubulointerstitial injury in proteinuric chronic kidney diseases.Frontiers in medicine · 2024Review
9 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
17 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
In chronic kidney disease (CKD), proteinuria results in severe tubulointerstitial lesions, which ultimately lead to end-stage renal disease. Here we identify 4-phenylbutyric acid (PBA), a chemical chaperone already used in humans, as a novel therapeutic strategy capable to counteract the toxic effect of proteinuria. Mechanistically, we show that albumin induces tubular unfolded protein response via cytosolic calcium rise, which leads to tubular apoptosis by Lipocalin 2 (LCN2) modulation through ATF4. Consistent with the key role of LCN2 in CKD progression, Lcn2 gene inactivation decreases ER stress-induced apoptosis, tubulointerstitial lesions and mortality in proteinuric mice. More importantly, the inhibition of this pathway by PBA protects kidneys from morphological and functional degradation in proteinuric mice. These results are relevant to human CKD, as LCN2 is increased in proteinuric patients. In conclusion, our study identifies a therapeutic strategy susceptible to improve the benefit of RAS inhibitors in proteinuria-induced CKD progression.
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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.