ArticleJournal of cellular and molecular medicine2017
The anti-ageing hormone klotho induces Nrf2-mediated antioxidant defences in human aortic smooth muscle cells.
Article in Journal of cellular and molecular medicine, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 67 papers.
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Who cites it
67 citing papers in PubMed, 106 citations in OpenAlex.
- Characterization of Umbilical Cord Mesenchymal Stromal Cells Overexpressing Klotho and In Vitro Anti-Aging Efficacy of Their Derived Extracellular Vesicles.International journal of molecular sciences · 2026Article
- Upregulated Klotho expression reflects a potential compensatory renal response in Trimethyltin-exposed rats.Medical molecular morphology · 2026Article
- Caffeic Acid Phenethyl Ester Enhanced the Klotho/SIRT1/Nrf2/HO-1 Axis to Protect Against Methylmercury-Induced ALS-Like Neurodegeneration.Molecular neurobiology · 2026Article
- Antiaging Properties of the Klotho Protein.Cells · 2026Review
- α-Klotho Supplementation Mitigates Cumulative Exercise-Induced Fatigue via Coordinated NRF2-Mediated Antioxidant Defense and AKT/GS-Driven Hepatic Glycogen Supercompensation in Mice.International journal of molecular sciences · 2025Article
- Vitamin D Protects Pancreatic Cancer (PC) Cells from Death and DNA Damage Induced by Oxidative Stress.Antioxidants (Basel, Switzerland) · 2025Article
- Klotho Suppresses Indoxyl Sulfate-Mediated Apoptosis in Human Kidney Proximal Tubular (HK-2) Cells through Modulating the AKT/Nrf2 Mechanism.ACS omega · 2025Article
- Klotho plasma levels are an independent predictorof mortality in women with acute coronary syndrome.Scientific reports · 2025Article
- Non-linear relationship between serum α-Klotho and suicide attempt: evidence from a large never-smoking population.BMC psychiatry · 2025Article
- Klotho alleviates oxidative stress and mitochondrial dysfunction through the Nrf2/HO-1 pathway, thereby reducing renal senescence induced by calcium oxalate crystals.Urolithiasis · 2025Article
- Pathophysiology of vascular ageing and the effect of novel cardio-renal protective medications in preventing progression of chronic kidney disease in people living with diabetes.Diabetic medicine : a journal of the British Diabetic Association · 2025Review
- Microvascular endothelial dysfunction in vascular senescence and disease.Frontiers in cardiovascular medicine · 2025Review
- AMP-dependent kinase stimulates the expression of αKlotho.FEBS open bio · 2024Article
- Effects of Life-Long Exercise on Age-Related Inflammation, Apoptosis, Oxidative Stress, Ferroptosis Markers, and NRF2/KAEP 1/Klotho Pathway in Rat Kidneys.Physiological research · 2024Article
- Review
- SARS-CoV-2 S Protein Reduces Cytoprotective Defenses and Promotes Human Endothelial Cell Senescence.Aging and disease · 2024Article
- Myocardial Expression of Pluripotency, Longevity, and Proinflammatory Genes in the Context of Hypercholesterolemia and Statin Treatment.Journal of clinical medicine · 2024Article
- FGF23 and klotho at the intersection of kidney and cardiovascular disease.Nature reviews. Cardiology · 2024Review
- A preliminary study of sirtuin-1 on angiotensin II-induced senescence and inflammation in abdominal aortic aneurysms.CytoJournal · 2024Article
- Association between serum Klotho levels and estimated pulse wave velocity in postmenopausal women: a cross-sectional study of NHANES 2007-2016.Frontiers in endocrinology · 2024Article
7 more citing papers are in PubMed but not listed here.
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Authors and funding
7 authors at 3 institutions in 2 countries.
Funding
Abstract
Vascular ageing in conditions such as atherosclerosis, diabetes and chronic kidney disease, is associated with the activation of the renin angiotensin system (RAS) and diminished expression of antioxidant defences mediated by the transcription factor nuclear factor erythroid 2-related factor 2 (Nrf2). The anti-ageing hormone klotho promotes longevity and protects against cardiovascular and renal diseases. Klotho has been shown to activate Nrf2 and attenuate oxidative damage in neuronal cells, however, the mechanisms by which it protects against vascular smooth muscle cell VSMC dysfunction elicited by Angiotensin II (AngII) remain to be elucidated. AngII contributes to vascular ageing and atherogenesis by enhancing VSMC oxidative stress, senescence and apoptosis. This study demonstrates that soluble klotho (1 nM, 24 hrs) significantly induces expression of Nrf2 and the antioxidant enzymes haeme oxygenase (HO-1) and peroxiredoxin-1 (Prx-1) and enhances glutathione levels in human aortic smooth muscle cells (HASMC). Silencing of Nrf2 attenuated the induction of HO-1 and Prx-1 expression by soluble klotho. Furthermore, soluble klotho protected against AngII-mediated HASMC apoptosis and senescence via activation of Nrf2. Thus, our findings highlight a novel Nrf2-mediated mechanism underlying the protective actions of soluble klotho in HAMSC. Targeting klotho may thus represent a therapeutic strategy against VSMC dysfunction and cardiovascular ageing.
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Registered trials
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