ArticleGastroenterology2010
Tumor necrosis factor and interferon-gamma down-regulate Klotho in mice with colitis.
Article in Gastroenterology, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 73 papers, 2 of them syntheses that pooled it.
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Who cites it
73 citing papers in PubMed, 2 syntheses or guidelines pooled it, 130 citations in OpenAlex.
- Effects of acute, subacute, and chronic exercise on plasma s-Klotho levels: a systematic review and meta-analysis.Journal of physiology and biochemistry · 2026Pooled it
- GWAS meta-analysis followed by Mendelian randomization revealed potential control mechanisms for circulating α-Klotho levels.Human molecular genetics · 2022Pooled it
- Extraintestinal Manifestations of Inflammatory Bowel Disease: A Focus on Kidney Complications.International journal of molecular sciences · 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
- 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
- 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
- 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
- Association between pan-immune-inflammation value and Serum Klotho levels: a cross-sectional analysis of renal function mediation.Frontiers in immunology · 2025Article
- Systemic immunoinflammatory indexes in albuminuric adults are negatively associated with α-klotho: evidence from NHANES 2007-2016.Renal failure · 2024Article
- Review
- Article
- Serum klotho concentrations in older men with hypertension or type 2 diabetes during prolonged exercise in temperate and hot conditions.European journal of applied physiology · 2023Article
- Recombinant Klotho attenuates IFNγ receptor signaling and SAMHD1 expression through blocking NF-κB translocation in glomerular mesangial cells.International journal of medical sciences · 2023Article
- Network-based quantitative trait linkage analysis of microbiome composition in inflammatory bowel disease families.Frontiers in genetics · 2023Article
- Alpha-Klotho in Parkinson's disease: a perspective on experimental evidence and potential clinical implications.Neural regeneration research · 2022Article
- Association between Dietary Inflammatory Index and serum Klotho concentration among adults in the United States.BMC geriatrics · 2022Article
- Klotho expression in peripheral blood circulating cells is associated with vascular and systemic inflammation in atherosclerotic vascular disease.Scientific reports · 2022Article
- Intestinal Inflammation Promotes MDL-1Cellular and molecular gastroenterology and hepatology · 2022Article
13 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
12 authors at 4 institutions in 3 countries.
Funding
Abstract
BACKGROUND &
aimsKlotho (KL) is an anti-inflammatory protein that protects the endothelium from nitric oxide (NO)-induced dysfunction, reduces the expression of endothelial adhesion molecules, and potentially regulates T-cell functions. KL deficiency leads to premature senescence and impaired Ca2+/Pi homeostasis, which can lead to inflammatory bowel disease (IBD)-associated osteopenia/osteoporosis. We investigated the changes in renal expression of Kl as a consequence of colitis.
methodsWe studied 3 mouse models of IBD: colitis induced by trinitrobenzene sulfonic acid, colitis induced by microflora (in gnotobiotic interleukin-10(-/-)), and colitis induced by adoptive transfer of CD4(+)CD45RB(high) T cells. Effects of the tumor necrosis factor (TNF) and interferon (IFN)-gamma on Kl expression and the activity of its promoter were examined in renal epithelial cells (mpkDCT4 and mIMCD3).
resultsRenal expression of Kl messenger RNA (mRNA) and protein was reduced in all 3 models of IBD. Reduced level of KL correlated with the severity of colitis; the effect was reversed by neutralizing antibodies against TNF. In vitro, TNF inhibited Kl expression, an effect potentiated by IFN-gamma. The combination of TNF and IFN-gamma increased expression of inducible nitric oxide synthase (iNOS) and increased NO production. The effect of IFN-gamma was reproduced by exposure to an NO donor and reversed by the iNOS inhibitor. In cells incubated with TNF and/or IFN-gamma, Kl mRNA stability was unaffected, whereas Kl promoter activity was reduced, indicating that these cytokines regulate Kl at the transcriptional level.
conclusionsThe down-regulation of KL that occurs during inflammation might account for the extraintestinal complications such as abnormalities in bone homeostasis that occur in patients with IBD.
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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.