ArticleOncotarget2017
Klotho suppresses the inflammatory responses and ameliorates cardiac dysfunction in aging endotoxemic mice.
Article in Oncotarget, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 50 papers, 1 of them a synthesis that pooled it.
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Who cites it
50 citing papers in PubMed, 1 synthesis or guideline pooled it, 85 citations in OpenAlex.
- A systematic review and meta-analysis demonstrating Klotho as an emerging exerkine.Scientific reports · 2022Pooled it
- Recombinant Klotho Protein Protects Tissues by Mitigating the Detrimental Effects of Sterile Inflammation After Hemorrhagic Shock.Shock (Augusta, Ga.) · 2026Article
- The Relationship Between Decreased Serum Klotho Protein and Cognitive Impairment in Patients After Abdominal Surgery.Journal of inflammation research · 2026Article
- Regulation of Klotho Production by Mineralocorticoid Receptor Signaling in Renal Cell Lines.Biomolecules · 2025Article
- Klotho: A multifaceted protector in sepsis-induced organ damage and a potential therapeutic target.World journal of critical care medicine · 2025Review
- Klotho modulation by tempol: a potential therapeutic axis in sepsis.BMC cardiovascular disorders · 2025Article
- Upregulation of TLR-MYD88 signaling, stem cell genes, and Klotho mediates sepsis-associated myocardial inflammation.Molecular biology reports · 2025Article
- Association between ethylene oxide exposure and Klotho levels in US adults.Scientific reports · 2025Article
- Klotho in age-related cardiovascular diseases: Insights into mitochondrial dysfunction and cell death.International journal of cardiology. Heart & vasculature · 2025Review
- Enhanced Therapeutic Effects of Human Mesenchymal stem Cells Transduced with Secreted Klotho in a Murine Experimental Autoimmune Encephalomyelitis Model.Molecular neurobiology · 2024Article
- The role of Klotho and sirtuins in sleep-related cardiovascular diseases: a review study.npj aging · 2024Review
- AMP-dependent kinase stimulates the expression of αKlotho.FEBS open bio · 2024Article
- Klotho and Clinical Outcomes in CKD: Findings From the Chronic Renal Insufficiency Cohort (CRIC) Study.American journal of kidney diseases : the official journal of the National Kidney Foundation · 2024Observational
- A comprehensive genetic map of cytokine responses in Lyme borreliosis.Nature communications · 2024Article
- Bioactive fiber-reinforced hydrogel to tailor cell microenvironment for structural and functional regeneration of myotendinous junction.Science advances · 2024Article
- Molecular Interaction of Soluble Klotho with FGF23 in the Pathobiology of Aortic Valve Lesions Induced by Chronic Kidney Disease.International journal of biological sciences · 2024Article
- Age-related matrix stiffening epigenetically regulates α-Klotho expression and compromises chondrocyte integrity.Nature communications · 2023Article
- Change in circulating klotho in response to weight loss, with and without exercise, in adults with overweight or obesity.Frontiers in aging · 2023Article
- The impact of SGLT2 inhibitors on αKlotho in renal MDCK and HK-2 cells.Frontiers in endocrinology · 2023Article
- The Interrelated Multifactorial Actions of Cortisol and Klotho: Potential Implications in the Pathogenesis of Parkinson's Disease.Brain sciences · 2022Review
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 2 countries.
Funding
Abstract
backgroundAging augments endotoxemic cardiac dysfunction, but the mechanism remains unclear. Anti-aging protein Klotho has been found to modulate tissue inflammatory responses. We tested the hypothesis that a reduced Klotho level in aging heart plays a role in the augmented endotoxemic cardiac dysfunction. MATERIALS AND
methodsEndotoxin (0.5 mg/kg, iv) was injected to adults (4-6 months) and aging (18-20 months) C57BL/6 mice. Recombinant Klotho (10 μg/kg, iv) was administered to a group of aging mice after endotoxin injection. Cardiac function was analyzed using a microcatheter at 24 and 48 h after endotoxin administration. Myocardial levels of Klotho and heat shock protein 70 (HSP70) were determined by immunoblotting, and plasma and myocardial cytokines were analyzed using ELISA.
resultsMore severe cardiac dysfunction in aging mice were accompanied by greater cytokine levels in the plasma and myocardium. Klotho was detected in the myocardial tissue. Klotho levels were lower in aging hearts and were further reduced during endotoxemia. Myocardial HSP70 levels were correlated with Klotho levels. Recombinant Klotho increased myocardial HSP70, inhibited NF-κB activation, reduced cytokine levels, and improved cardiac function in aging endotoxemic mice. Delivery of HSP70 into cultured macrophages suppressed endotoxin-induced NF-κB activation.
conclusionsAging-related augmentation of inflammatory responses and cardiac dysfunction is associated with relative Klotho deficiency. Post-treatment with recombinant Klotho suppresses the inflammatory responses and improves cardiac function in aging endotoxemic mice. Klotho modulates HSP70 levels and HSP70 appears to be involved in the anti-inflammatory mechanism of Klotho. Klotho may have therapeutic potential in amelioration of aging-related endotoxemic cardiac dysfunction.
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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.