ArticleNephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association2023
The direct effect of fibroblast growth factor 23 on vascular smooth muscle cell phenotype and function.
Article in Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers, 1 of them a synthesis that pooled it.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
18 citing papers in PubMed, 1 synthesis or guideline pooled it, 22 citations in OpenAlex.
- Role of klotho and fibroblast growth factor 23 in arterial calcification, thickness, and stiffness: a meta-analysis of observational studies.Scientific reports · 2024Pooled it
- Broken signals: when the mineralostat alters the cardiovascular system.Pediatric nephrology (Berlin, Germany) · 2026Review
- The Impact of Hyperphosphatemia on Mineral and Bone Metabolism: Implications for Bone and Vascular Health.International journal of molecular sciences · 2026Review
- 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
- Mechanisms of vascular calcification: cellular phenotype switching drives matrix remodeling and mineralized microenvironment formation.Frontiers in cardiovascular medicine · 2026Review
- A guide to uraemic toxicity.Nature reviews. Nephrology · 2026Review
- Phosphate and Inflammation in Health and Kidney Disease.International journal of molecular sciences · 2025Review
- Fibroblast growth factor-23 remodels vascular extracellular matrix via glycosaminoglycan induction: implications for calcification in chronic kidney disease.Renal failure · 2025Article
- La Ribonucleoprotein 7 Protects Vascular Smooth Muscle Cell Contractile Phenotype in CKD by Coupling with P300.Journal of the American Society of Nephrology : JASN · 2025Article
- Impacts of systemic milieu on cerebrovascular and brain aging: insights from heterochronic parabiosis, blood exchange, and plasma transfer experiments.GeroScience · 2025Review
- New biomarkers of inflammation associated with haemodialysis.Clinical kidney journal · 2025Article
- Office Blood Pressure and Obesity in Children with X-Linked Hypophosphatemia.Calcified tissue international · 2025Observational
- The true cost of phosphate control in chronic kidney disease.Clinical kidney journal · 2025Article
- Fibroblast Growth Factor 21 Promotes Vascular Smooth Muscle Cell Contractile Polarization via p38 Mitogen-Activated Protein Kinase-Promoted Serum Response Factor Phosphorylation.Research (Washington, D.C.) · 2025Article
- Role of Uremic Toxins in Vascular Inflammation Associated with Chronic Kidney Disease.Journal of clinical medicine · 2024Article
- Diabetes mellitus modifies the association between chronic kidney disease-mineral and bone disorder biomarkers and aortic stiffness in peritoneal dialysis patients.Scientific reports · 2024Article
- Role of kidney transplantation in long-term cardiac reverse remodeling and interconnecting mechanisms in type 4 cardiorenal syndrome.Frontiers in nephrology · 2024Article
- Dietary Mg Supplementation Decreases Oxidative Stress, Inflammation, and Vascular Dysfunction in an Experimental Model of Metabolic Syndrome with Renal Failure.Antioxidants (Basel, Switzerland) · 2023Article
Corrections and comments
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Authors and funding
20 authors at 9 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundIn chronic kidney disease (CKD) patients, increased levels of fibroblast growth factor 23 (FGF23) are associated with cardiovascular mortality. The relationship between FGF23 and heart hypertrophy has been documented, however, it is not known whether FGF23 has an effect on vasculature. Vascular smooth muscle cells VSMCs may exhibit different phenotypes; our hypothesis is that FGF23 favours a switch from a contractile to synthetic phenotype that may cause vascular dysfunction. Our objective was to determine whether FGF23 may directly control a change in VSMC phenotype.
methodsThis study includes in vitro, in vivo and ex vivo experiments and evaluation of patients with CKD stages 2-3 studying a relationship between FGF23 and vascular dysfunction.
resultsIn vitro studies show that high levels of FGF23, by acting on its specific receptor FGFR1 and Erk1/2, causes a change in the phenotype of VSMCs from contractile to synthetic. This change is mediated by a downregulation of miR-221/222, which augments the expression of MAP3K2 and PAK1. miR-221/222 transfections recovered the contractile phenotype of VSMCs. Infusion of recombinant FGF23 to rats increased vascular wall thickness, with VSMCs showing a synthetic phenotype with a reduction of miR-221 expression. Ex-vivo studies on aortic rings demonstrate also that high FGF23 increases arterial stiffening. In CKD 2-3 patients, elevation of FGF23 was associated with increased pulse wave velocity and reduced plasma levels of miR-221/222.
conclusionIn VSMCs, high levels of FGF23, through the downregulation of miR-221/222, causes a change to a synthetic phenotype. This change in VSMCs increases arterial stiffening and impairs vascular function, which might ultimately worsen cardiovascular disease.
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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 Socratic graph.