ArticleJournal of the American Society of Nephrology : JASN2011
The inflammatory cytokines TWEAK and TNFα reduce renal klotho expression through NFκB.
Article in Journal of the American Society of Nephrology : JASN, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT04936282 (Treatment of Early Borderline Lesions in Low Immunological Risk Kidney Transplant Patients), which is not on this map. Cited by 207 papers, 1 of them a synthesis 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.
Treatment of Early Borderline Lesions in Low Immunological Risk Kidney Transplant Patients: a Spanish Multicenter, Randomized, Controlled Parallel-group Trial: The TRAINING Study
Who cites it
207 citing papers in PubMed, 1 synthesis or guideline pooled it, 384 citations in OpenAlex.
- GWAS meta-analysis followed by Mendelian randomization revealed potential control mechanisms for circulating α-Klotho levels.Human molecular genetics · 2022Pooled it
- Trial
- Visceral Adiposity and Renal Health: From Pathophysiological Mechanisms to Novel Therapeutic Strategies.Journal of clinical medicine · 2026Review
- Anti-aging effects of glycyrrhizin via maintaining Klotho levels.Journal of clinical biochemistry and nutrition · 2026Article
- Review
- Ten Hot Topics in Cardiovascular Risk Management for Chronic Kidney Disease.Cardiorenal medicine · 2026Review
- Serum α-Klotho and SIRT1 - Relationship with graft function, inflammation and hospitalization rates in kidney transplant recipients.Transplant international : official journal of the European Society for Organ Transplantation · 2026Observational
- Remote ischemic per-conditioning did not modulate kidney Klotho expression in acute kidney injury induced by renal ischemia/reperfusion injury.BMC nephrology · 2025Article
- [Potential of early diagnosis and targeted therapy for Klotho protein in chronic kidney disease].Zhong nan da xue xue bao. Yi xue ban = Journal of Central South University. Medical sciences · 2025Review
- Klotho: A multifaceted protector in sepsis-induced organ damage and a potential therapeutic target.World journal of critical care medicine · 2025Review
- A High-Fat Diet Increases Kidney Fibrosis Through Regulating TGF-β and PDGF-β Signaling Pathways in Normotensive and Hypertensive Rat Models.International journal of molecular sciences · 2025Article
- State of the art: Renal recovery after AKI - from basic science to clinical practice.Intensive care medicine · 2025Review
- The role of the intestinal microbiome in cognitive decline in patients with kidney disease.Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association · 2025Review
- Exploring the Associations Between Inflammatory Biomarkers, Survival, and Cardiovascular Events in Hemodialysis Patients and the Interrelationship with Nutritional Parameters-The Experience of a Single Transylvanian Dialysis Center.Journal of clinical medicine · 2025Article
- Sex differences in the association between serum α-Klotho levels and hyperlipidemia: a cross-sectional study from NHANES 2013-2016.Scientific reports · 2025Article
- Systemic immune-inflammation index mediates the association between abdominal obesity and serum klotho levels.Scientific reports · 2025Article
- The Impact of Klotho in Cancer: From Development and Progression to Therapeutic Potential.Genes · 2025Review
- Associations of weight-adjusted-waist index and systemic immune-inflammatory index with sKlotho: evidence from the NHANES 2007-2016.Frontiers in endocrinology · 2025Article
- Astragaloside IV Improves Diabetic Kidney Disease by Regulating NLRP3 Inflammasome.Journal of diabetes research · 2025Review
- Association between pan-immune-inflammation value and Serum Klotho levels: a cross-sectional analysis of renal function mediation.Frontiers in immunology · 2025Article
147 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
13 authors at 7 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Proinflammatory cytokines contribute to renal injury, but the downstream effectors within kidney cells are not well understood. One candidate effector is Klotho, a protein expressed by renal cells that has antiaging properties; Klotho-deficient mice have an accelerated aging-like phenotype, including vascular injury and renal injury. Whether proinflammatory cytokines, such as TNF and TNF-like weak inducer of apoptosis (TWEAK), modulate Klotho is unknown. In mice, exogenous administration of TWEAK decreased expression of Klotho in the kidney. In the setting of acute kidney injury induced by folic acid, the blockade or absence of TWEAK abrogated the injury-related decrease in renal and plasma Klotho levels. TWEAK, TNFα, and siRNA-mediated knockdown of IκBα all activated NFκB and reduced Klotho expression in the MCT tubular cell line. Furthermore, inhibition of NFκB with parthenolide prevented TWEAK- or TNFα-induced downregulation of Klotho. Inhibition of histone deacetylase reversed TWEAK-induced downregulation of Klotho, and chromatin immunoprecipitation showed that TWEAK promotes RelA binding to the Klotho promoter, inducing its deacetylation. In conclusion, inflammatory cytokines, such as TWEAK and TNFα, downregulate Klotho expression through an NFκB-dependent mechanism. These results may partially explain the relationship between inflammation and diseases characterized by accelerated aging of organs, including CKD.
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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.