ArticleThe Journal of clinical investigation2003
Secreted frizzled-related protein 4 is a potent tumor-derived phosphaturic agent.
Article in The Journal of clinical investigation, 2003. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT00099762 (Selective Venous Catheterization for the Localization of Phosphaturic Mesenchymal Tumors), which is not on this map. Cited by 78 papers.
What it found
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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.
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.
Selective Venous Catheterization for the Localization of Phosphaturic Mesenchymal Tumors
Who cites it
78 citing papers in PubMed, 292 citations in OpenAlex.
- Phosphate Concentrations and Modifying Factors in Healthy Children From 12 to 24 Months of Age.The Journal of clinical endocrinology and metabolism · 2021Trial
- Phosphate: An Anion Controlling Metabolic Functions.Nutrients · 2026Review
- Recent research progress on the etiology and pathogenesis of tumor-induced osteomalacia: A review.Journal of bone oncology · 2026Review
- The Janus Face of sFRP4 in Cancer: From Mechanistic Complexity to Therapeutic Potential.International journal of molecular sciences · 2026Review
- Case Report: Phosphaturic mesenchymal tumor presenting solely as knee pain without hypophosphatemia.Frontiers in oncology · 2025Article
- The Intricacies of Renal Phosphate Reabsorption-An Overview.International journal of molecular sciences · 2024Review
- A 50-Year-Old Man Presenting with Multiple Bone Lesions and a Diagnosis of Phosphaturic Mesenchymal Tumor of the Femur.The American journal of case reports · 2024Article
- Phosphaturic Mesenchymal Tumors with or without Phosphate Metabolism Derangements.Current oncology (Toronto, Ont.) · 2023Review
- The contribution of a novelFrontiers in endocrinology · 2023Article
- Bioinformatics Analysis of Common Differential Genes of Viral Myocarditis and Dilated Cardiomyopathy: Screening for Potential Pharmacological Compounds.Journal of cardiovascular development and disease · 2022Article
- [Tumor localization and treatment of tumor-induced osteomalacia].Zeitschrift fur Rheumatologie · 2022Review
- Hypophosphatemia in acute liver failure of a broad range of etiologies is associated with phosphaturia without kidney damage or phosphatonin elevation.Translational research : the journal of laboratory and clinical medicine · 2021Article
- A supergene underlies linked variation in color and morphology in a Holarctic songbird.Nature communications · 2021Article
- The Causes of Hypo- and Hyperphosphatemia in Humans.Calcified tissue international · 2021Review
- Reduction of Secreted Frizzled-Related Protein 5 Drives Vascular Calcification through Wnt3a-Mediated Rho/ROCK/JNK Signaling in Chronic Kidney Disease.International journal of molecular sciences · 2020Article
- Frequent overexpression of klotho in fusion-negative phosphaturic mesenchymal tumors with tumorigenic implications.Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc · 2020Article
- Article
- FGF23 and Associated Disorders of Phosphate Wasting.Pediatric endocrinology reviews : PER · 2019Review
- Mechanisms of phosphate transport.Nature reviews. Nephrology · 2019Review
- Tumor-induced osteomalacia: experience from three tertiary care centers in India.Endocrine connections · 2019Article
18 more citing papers are in PubMed but not listed here.
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Authors and funding
9 authors at 3 institutions in 1 country.
Funding
Abstract
Tumors associated with osteomalacia elaborate the novel factor(s), phosphatonin(s), which causes phosphaturia and hypophosphatemia by cAMP-independent pathways. We show that secreted frizzled-related protein-4 (sFRP-4), a protein highly expressed in such tumors, is a circulating phosphaturic factor that antagonizes renal Wnt-signaling. In cultured opossum renal epithelial cells, sFRP-4 specifically inhibited sodium-dependent phosphate transport. Infusions of sFRP-4 in normal rats over 2 hours specifically increased renal fractional excretion of inorganic phosphate (FEPi) from 14% +/- 2% to 34% +/- 5% (mean +/- SEM, P < 0.01). Urinary cAMP and calcium excretion were unchanged. In thyro-parathyroidectomized rats, sFRP-4 increased FEPi from 0.7% +/- 0.2% to 3.8% +/- 1.2% (P < 0.05), demonstrating that sFRP-4 inhibits renal inorganic phosphate reabsorption by PTH-independent mechanisms. Administration of sFRP-4 to intact rats over 8 hours increased FEPi, decreased serum phosphate (1.95 +/- 0.1 to 1.53 +/- 0.09 mmol/l, P < 0.05) but did not alter serum 1alpha, 25-dihydroxyvitamin D, renal 25-hydroxyvitamin D 1alpha-hydroxylase cytochrome P450, and sodium-phosphate cotransporter mRNA concentrations. Infusion of sFRP-4 antagonizes Wnt action as demonstrated by reduced renal beta-catenin and increased phosphorylated beta-catenin concentrations. The sFRP-4 is detectable in normal human serum and in the serum of a patient with tumor-induced osteomalacia. Thus, sFRP-4 displays phosphatonin-like properties, because it is a circulating protein that promotes phosphaturia and hypophosphatemia and blunts compensatory increases in 1alpha, 25-dihydroxyvitamin D.
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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 OpenQuestion graph.