ReviewFrontiers in cardiovascular medicine2020
Shedding of Klotho: Functional Implications in Chronic Kidney Disease and Associated Vascular Disease.
Review in Frontiers in cardiovascular medicine, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 42 citations in OpenAlex.
- Pharmaceutical Strategies for Translating Klotho-Based Therapeutics: From Biologic Developability to Advanced Delivery Systems.Pharmaceutics · 2026Review
- Antiaging Properties of the Klotho Protein.Cells · 2026Review
- Ion channels and cardiac disease: mechanisms and functions of a disintegrin and metalloproteases and their substrates.Frontiers in cell and developmental biology · 2026Review
- Growth hormone treatment associates with improved circulating anti-aging protein Klotho and reduced arterial stiffness in children with CKD.Clinical kidney journal · 2025Article
- ADAM10-mediated β-klotho degradation: a key to FGF21 resistance in senescent vascular endothelial cells.GeroScience · 2025Article
- Soluble average Klotho level as a prognostic marker for acute kidney injury outcomes: a 90-day follow-up study.Biomarkers in medicine · 2025Article
- Involvement of ADAM17-Klotho Crosstalk in High Glucose-Induced Alterations of Podocyte Function.International journal of molecular sciences · 2025Article
- Review
- Klotho: molecular mechanisms and emerging therapeutics in central nervous system diseases.Molecular biology reports · 2024Review
- Linear-inverse associations of serum Klotho protein with prevalence of frailty among adults in the United States.American journal of translational research · 2024Article
- Klotho: a potential therapeutic target in aging and neurodegeneration beyond chronic kidney disease-a comprehensive review from the ERA CKD-MBD working group.Clinical kidney journal · 2024Article
- The Importance of α-Klotho in Depression and Cognitive Impairment and Its Connection to Glutamate Neurotransmission-An Up-to-Date Review.International journal of molecular sciences · 2023Review
- Role of Chronic Kidney Disease (CKD)-Mineral and Bone Disorder (MBD) in the Pathogenesis of Cardiovascular Disease in CKD.Journal of atherosclerosis and thrombosis · 2023Review
- ADAM10 and ADAM17, Major Regulators of Chronic Kidney Disease Induced Atherosclerosis?International journal of molecular sciences · 2023Review
- Adherence to Mediterranean Diet and Soluble Klotho Level: The Value of Food Synergy in Aging.Nutrients · 2022Article
- KL1 Domain of Longevity Factor Klotho Mimics the Metabolome of Cognitive Stimulation and Enhances Cognition in Young and Aging Mice.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2022Article
- Klotho an Autophagy Stimulator as a Potential Therapeutic Target for Alzheimer's Disease: A Review.Biomedicines · 2022Review
- Genes and Longevity of Lifespan.International journal of molecular sciences · 2022Review
- Proteolysis dysfunction in the process of aging and age-related diseases.Frontiers in aging · 2022Review
- The Relationship Between Klotho and SIRT1 Expression in Renal Aging Related Disease.International journal of general medicine · 2022Article
Corrections and comments
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Authors and funding
3 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
α-Klotho (Klotho) exists in two different forms, a membrane-bound and soluble form, which are highly expressed in the kidney. Both forms play an important role in various physiological and pathophysiological processes. Recently, it has been identified that soluble Klotho arises exclusively from shedding or proteolytic cleavage. In this review, we will highlight the mechanisms underlying the shedding of Klotho and the functional effects of soluble Klotho, especially in CKD and the associated cardiovascular complications. Klotho can be cleaved by a process called shedding, releasing the ectodomain of the transmembrane protein. A disintegrin and metalloproteases ADAM10 and ADAM17 have been demonstrated to be mainly responsible for this shedding, resulting in either full-length fragments or sub-fragments called KL1 and KL2. Reduced levels of soluble Klotho have been associated with kidney disease, especially chronic kidney disease (CKD). In line with a protective effect of soluble Klotho in vascular function and calcification, CKD and the reduced levels of soluble Klotho herein are associated with cardiovascular complications. Interestingly, although it has been demonstrated that soluble Klotho has a multitude of effects its direct impact on vascular cells and the exact underlying mechanisms remain largely unknown and should therefore be a major focus of further research. Moreover, functional implications of the cleavage process resulting in KL1 and KL2 fragments remain to be elucidated.
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