ArticleAging2020
Klotho alleviates indoxyl sulfate-induced heart failure and kidney damage by promoting M2 macrophage polarization.
Article in Aging, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 37 papers.
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Who cites it
37 citing papers in PubMed, 66 citations in OpenAlex.
- Pentoxifylline ameliorates subclinical atherosclerosis progression in patients with type 2 diabetes and chronic kidney disease: a randomized pilot trial.Cardiovascular diabetology · 2024Trial
- Gut microbiota-derived metabolites as immune modulators in aging and age-related chronic inflammatory diseases.Ageing research reviews · 2026Review
- Bridging gut microbiota and renal health: Klotho as a promising therapeutic agent in DKD.Naunyn-Schmiedeberg's archives of pharmacology · 2026Review
- State of the art: Renal recovery after AKI - from basic science to clinical practice.Intensive care medicine · 2025Review
- Klotho Suppresses Indoxyl Sulfate-Mediated Apoptosis in Human Kidney Proximal Tubular (HK-2) Cells through Modulating the AKT/Nrf2 Mechanism.ACS omega · 2025Article
- Renal-Cardiac Crosstalk in the Pathogenesis and Progression of Heart Failure.Circulation research · 2025Review
- Klotho in age-related cardiovascular diseases: Insights into mitochondrial dysfunction and cell death.International journal of cardiology. Heart & vasculature · 2025Review
- Klotho antiaging protein: molecular mechanisms and therapeutic potential in diseases.Molecular biomedicine · 2025Review
- Mechanisms and Prevention Strategies of Macrophage Involvement in the Progression From Hypertension to Heart Failure.International journal of hypertension · 2025Review
- Identification of Necroptosis and Immune Infiltration in Heart Failure Through Bioinformatics Analysis.Journal of inflammation research · 2025Article
- Inflammation-Induced Klotho Deficiency: A Possible Key Driver of Chronic Kidney Disease Progression.International journal of general medicine · 2025Review
- Uremic Toxin Receptor AhR Facilitates Renal Senescence and Fibrosis via Suppressing Mitochondrial Biogenesis.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- Article
- Indoxyl sulphate-TNFα axis mediates uremic encephalopathy in rodent acute kidney injury.Acta pharmacologica Sinica · 2024Article
- Indoxyl Sulfate-Induced Macrophage Toxicity and Therapeutic Strategies in Uremic Atherosclerosis.Toxins · 2024Review
- Bioactive fiber-reinforced hydrogel to tailor cell microenvironment for structural and functional regeneration of myotendinous junction.Science advances · 2024Article
- Uremic toxins mediate kidney diseases: the role of aryl hydrocarbon receptor.Cellular & molecular biology letters · 2024Review
- Relationship between Serum Indoxyl Sulfate and Klotho Protein and Vascular Calcification in Patients with Chronic Kidney Disease Stages 3-5.International journal of endocrinology · 2024Article
- Fibroblast growth factor signaling in macrophage polarization: impact on health and diseases.Frontiers in immunology · 2024Review
- Role of macrophage polarization in heart failure and traditional Chinese medicine treatment.Frontiers in pharmacology · 2024Review
Corrections and comments
- Erratum issued
Authors and funding
4 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Indoxyl sulfate (IS) is a protein-bound uremic toxin that can accumulate in patients with chronic kidney disease (CKD) or acute kidney injury (AKI) and cause kidney and cardiac dysfunction. Klotho is an anti-aging protein that has reno- and cardio-protective effects. We investigated whether Klotho could alleviate IS-induced heart failure and kidney damage by regulating macrophages, which play a key role in the inflammatory response in CKD and AKI. Treatment of THP-1-derived macrophages with IS induced the production of the pro-inflammatory cytokines TNFα, IL-6, and IL-1β, and stimulated M1 polarization. Additionally, IS induced downregulation of Klotho expression in macrophages. Overexpression of Klotho suppressed the IS-induced inflammatory response in macrophages by stimulating M2 polarization. It also alleviated IS-induced cardiac hypertrophy and renal fibrosis in mice. A reduction in IS-induced phosphorylation of NF-kB p65 was observed in response to Klotho overexpression, suggesting that Klotho alleviates kidney and cardiac injury by inactivating NF-kB signaling and promoting macrophage M2 polarization.
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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.