ArticleFrontiers in pharmacology2020
High Phosphate Induces and Klotho Attenuates Kidney Epithelial Senescence and Fibrosis.
Article in Frontiers in pharmacology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.
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Who cites it
37 citing papers in PubMed, 40 citations in OpenAlex.
- Traditional Chinese Medicine Formulas in Delaying Aging: From Theoretical Foundations to Molecular Mechanisms and Translational Perspectives.Journal of cellular and molecular medicine · 2026Review
- Article
- Correcting serum phosphate homeostasis does not alleviate the health dangers of high phosphate consumption.Journal of translational medicine · 2026Article
- Hyperbranched poly(β-amino ester)s-mediated delivery of engineered Klotho mRNA rescues senescence and restores cellular homeostasis in aged and Klotho deficient iMSCs.Drug delivery and translational research · 2026Article
- DNA hypermethylation of FGFR2 drives fibrosis in the aging kidney.Scientific reports · 2026Article
- The effects of elevated phosphate on the kidney - damaging the gatekeeper.Pflugers Archiv : European journal of physiology · 2026Review
- Sustained and reversible effects of a dietary phosphate intake on bone and mineral metabolism during aging.GeroScience · 2026Article
- High-Phosphate-Induced Hypertension: The Pathogenic Role of Fibroblast Growth Factor 23 (FGF23) Signaling in Sympathetic Nervous System Activation.International journal of molecular sciences · 2026Review
- Prognostic Analysis of ICU Patients with Chronic Obstructive Pulmonary Disease Based on Blood Phosphate Dynamics: A Retrospective Cohort Study from the MIMIC-IV Database.International journal of chronic obstructive pulmonary disease · 2026Article
- Cinacalcet Efficacy in Hyperparathyroidism-Chronic Kidney Disease-Non-Dialysis, Hemodialysis, Peritoneal Dialysis, Kidney Transplantation: Critical Review.Biomedicines · 2025Review
- The anti-aging Klotho protects glioblastoma macrophages from radiotherapy-induced inflammation and predicts immunotherapy response.International journal of cancer · 2025Article
- Hyperphosphatemia in Kidney Failure: Pathophysiology, Challenges, and Critical Role of Phosphorus Management.Nutrients · 2025Review
- Update of cellular senescence in kidney fibrosis: from mechanism to potential interventions.Frontiers of medicine · 2025Review
- Targeting senescence to prevent diabetic kidney disease: Exploring molecular mechanisms and potential therapeutic targets for disease management.Diabetic medicine : a journal of the British Diabetic Association · 2025Review
- Targeting cellular senescence in kidney diseases and aging: A focus on mesenchymal stem cells and their paracrine factors.Cell communication and signaling : CCS · 2024Review
- A signaling pathway map of plasminogen activator inhibitor-1 (PAI-1/SERPINE-1): a review of an innovative frontier in molecular aging and cellular senescence.Cell communication and signaling : CCS · 2024Review
- Women With a History of Preeclampsia Exhibit Accelerated Aging and Unfavorable Profiles of Senescence Markers.Hypertension (Dallas, Tex. : 1979) · 2024Article
- Association Between the Serum Phosphate Levels and Hospital Mortality as Well as 90-Day Mortality Among Critically Ill Patients with Chronic Obstructive Pulmonary Disease: A Retrospective Cohort Study.International journal of chronic obstructive pulmonary disease · 2024Article
- Cellular senescence and kidney aging.Clinical science (London, England : 1979) · 2023Review
- Relationships between blood bone metabolic biomarkers and anemia in patients with chronic kidney disease.Renal failure · 2023Article
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
Abstract
Cellular senescence is an irreversible cell growth arrest and is associated with aging and age-related diseases. High plasma phosphate (Pi) and deficiency of Klotho contribute to aging and kidney fibrosis, a pathological feature in the aging kidney and chronic kidney disease. This study examined the interactive role of Pi and Klotho in kidney senescence and fibrosis. Homozygous Klotho hypomorphic mice had high plasma Pi, undetectable Klotho in plasma and kidney, high senescence with massive collagen accumulation in kidney tubules, and fibrin deposits in peritubular capillaries. To examine the Pi effect on kidney senescence, a high (2%) Pi diet was given to wild-type mice. One week of high dietary Pi mildly increased plasma Pi, and upregulated kidney p16/p21 expression, but did not significantly decrease Klotho. Two weeks of high Pi intake led to increase in plasminogen activator inhibitor (PAI)-1, and decrease in kidney Klotho, but still without detectable increase in kidney fibrosis. More prolonged dietary Pi for 12 weeks exacerbated kidney senescence and fibrosis; more so in heterozygous Klotho hypomorphic mice compared to wild-type mice, and in mice with chronic kidney disease (CKD) on high Pi diet compared to CKD mice fed a normal Pi diet. In cultured kidney tubular cells, high Pi directly induced cellular senescence, injury and epithelial-mesenchymal transition, and enhanced H
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