ArticleJournal of molecular and cellular cardiology2020
FGF23 induced left ventricular hypertrophy mediated by FGFR4 signaling in the myocardium is attenuated by soluble Klotho in mice.
Article in Journal of molecular and cellular cardiology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 50 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
50 citing papers in PubMed, 78 citations in OpenAlex.
- Trial
- Exploring the Association of Angiotensin-(1-7) with Left Ventricular Mass Index in Youth with Hereditary Hypophosphatemia: A Pilot Study.Research square · 2026Article
- Gestational diabetes as an inter-generational cardiometabolic risk factor: spotlight on emerging exerkines.Cardiovascular diabetology · 2026Review
- Chronic kidney disease-associated cardiomyopathy: clinical features, pathophysiology and treatment.Nature reviews. Cardiology · 2026Review
- Review
- 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
- Chronic Kidney Disease in Patients With Heart Failure With a Preserved Ejection Fraction: The Underlying Role of Visceral Adiposity.Journal of the American College of Cardiology · 2025Review
- High Dietary Phosphate Intake Induces Hypertension and Sympathetic Overactivation via Central Fibroblast Growth Factor Receptor Signaling.Circulation · 2025Article
- Genetic deletion of the sodium phosphate cotransporter NaPi2a ameliorates heart failure in mice.Scientific reports · 2025Article
- Intersecting Pathways of Inflammation, Oxidative Stress, and Atherogenesis in the Evaluation of CKD: Emerging Biomarkers PCSK9, EPHX2, AOPPs, and TBARSs.Life (Basel, Switzerland) · 2025Review
- Fibroblast growth factor 23 and fibroblast growth factor receptor 4 promote cardiac metabolic remodeling in chronic kidney disease.Kidney international · 2025Article
- Klotho Is Cardioprotective in the mdx Mouse Model of Duchenne Muscular Dystrophy.The American journal of pathology · 2025Article
- Baseline fibroblast growth factor 23 predicts incident heart failure and cardiovascular mortality in patients with chronic kidney disease: A 3-year follow-up study.International journal of cardiology. Heart & vasculature · 2025Article
- Specific associations of serum FGF23 and soluble Klotho with different types of left ventricular hypertrophy in hypertensive peritoneal dialysis patients: a cross-sectional study.Frontiers in cardiovascular medicine · 2025Article
- Emerging concepts on the FGF23 regulation and activity.Molecular and cellular biochemistry · 2025Review
- The role of fibroblast growth factor 23 in regulation of phosphate balance.Pediatric nephrology (Berlin, Germany) · 2024Review
- Klotho enhances diastolic function in aged hearts through Sirt1-mediated pathways.GeroScience · 2024Article
- S100a8/9 (S100 Calcium Binding Protein a8/9) Promotes Cardiac Hypertrophy Via Upregulation of FGF23 (Fibroblast Growth Factor 23) in Mice.Journal of the American Heart Association · 2024Article
- Article
- FGF23 and klotho at the intersection of kidney and cardiovascular disease.Nature reviews. Cardiology · 2024Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
There is controversy regarding whether excess FGF23 causes left ventricular hypertrophy (LVH) directly through activation of fibroblast growth factor receptor 4 (FGFR4) in cardiomyocytes or indirectly through reductions in soluble Klotho (sK). We investigated the respective roles of myocardial FGFR4 and sKL in mediating FGF23-induced LVH using mouse genetic and pharmacological approaches. To investigate a direct role of myocardial FGFR4 in mediating the cardiotoxic effects of excess circulating FGF23, we administered rFGF23 to mice with cardiac-specific loss of FGFR4 (FGFR4 heart-cKO). We tested a model of sKL deficiency, hypertension and LVH created by the conditional deletion of FGFR1 in the renal distal tubule (FGFR1DT cKO mice). The cardioprotective effects of sKL in both mouse models was assessed by the systemic administration of recombinant sKL. We confirmed that FGF23 treatment activates PLCγ in the heart and induces LVH in the absence of membrane α-Klotho. Conditional deletion of FGFR4 in the myocardium prevented rFGF23-induced LVH in mice, establishing direct cardiotoxicity of FGF23 through activation of FGFR4. Recombinant sKL administration prevented LVH, but not HTN, in FGFR1DT cKO mice, consistent with direct cardioprotective effects. Co-administration of recombinant sKL with FGF23 in culture inhibited rFGF23-induced p-PLCγ signaling. Thus, FGF23 ability to include LVH represents a balance between FGF23 direct cardiac activation of FGFR4 and the modulating effects of circulating sKL to alter FGF23-dependent myocardial signaling pathways.
Indexed as
Identifiers
What OpenQuestion holds
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.