ArticleFASEB journal : official publication of the Federation of American Societies for Experimental Biology2009
In vivo genetic evidence for klotho-dependent, fibroblast growth factor 23 (Fgf23) -mediated regulation of systemic phosphate homeostasis.
Article in FASEB journal : official publication of the Federation of American Societies for Experimental Biology, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 146 papers.
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Who cites it
146 citing papers in PubMed, 251 citations in OpenAlex.
- FGF23, Frailty, and Falls in SPRINT.Journal of the American Geriatrics Society · 2021Trial
- Serum Phosphorus and Risk of Cardiovascular Disease, All-Cause Mortality, or Graft Failure in Kidney Transplant Recipients: An Ancillary Study of the FAVORIT Trial Cohort.American journal of kidney diseases : the official journal of the National Kidney Foundation · 2017Trial
- Can salivary phosphate levels be an early biomarker to monitor the evolvement of obesity?Contributions to nephrology · 2013Trial
- Bone transcriptomics reveals that juzentaihoto remodels and activates multiple pathways in Klotho-deficient mice.Bone reports · 2026Article
- Age-Related Hyperphosphatemia Is Associated with Metabolic and Mitochondrial Alterations During Myogenic Differentiation and in Skeletal Muscle from Old Mice.International journal of molecular sciences · 2026Article
- Soft tissue calcifications in chronic kidney disease-beyond the vasculature.Pflugers Archiv : European journal of physiology · 2025Review
- Preeclampsia as a Study Model for Aging: The Klotho Gene Paradigm.International journal of molecular sciences · 2025Review
- Association of hyperphosphatemia with renal prognosis in patients with autosomal dominant polycystic kidney disease.Clinical and experimental nephrology · 2025Article
- The role of fibroblast growth factor 23 in regulation of phosphate balance.Pediatric nephrology (Berlin, Germany) · 2024Review
- Hyperphosphatemia Contributes to Skeletal Muscle Atrophy in Mice.International journal of molecular sciences · 2024Article
- Skeletal Muscle Injury in Chronic Kidney Disease-From Histologic Changes to Molecular Mechanisms and to Novel Therapies.International journal of molecular sciences · 2024Review
- C-terminal fragment of fibroblast growth factor 23 improves heart function in murine models of high intact fibroblast growth factor 23.American journal of physiology. Renal physiology · 2024Article
- Gα11 deficiency increases fibroblast growth factor 23 levels in a mouse model of familial hypocalciuric hypercalcemia.JCI insight · 2024Article
- FGF23 and klotho at the intersection of kidney and cardiovascular disease.Nature reviews. Cardiology · 2024Review
- Distinct role of Klotho in long bone and craniofacial bone: skeletal development, repair and regeneration.PeerJ · 2024Review
- Relationship of the bone phenotype of the Klotho mutant mouse model of accelerated aging to changes in skeletal architecture that occur with chronological aging.Frontiers in endocrinology · 2024Article
- Fibroblast Growth Factor 23 and Muscle Wasting: A Metabolic Point of View.Kidney international reports · 2023Review
- Regulation of FGF23 production and phosphate metabolism by bone-kidney interactions.Nature reviews. Nephrology · 2023Review
- FGF-23 protects cell function and viability in murine pancreatic islets challenged by glucolipotoxicity.Pflugers Archiv : European journal of physiology · 2023Article
- Article
86 more citing papers are in PubMed but not listed here.
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Authors and funding
9 authors at 4 institutions in 2 countries.
Funding
Abstract
A major breakthrough in systemic phosphate homeostasis regulation was achieved by the demonstration of strikingly similar physical, morphological, and biochemical phenotypes of fibroblast growth factor 23 (Fgf23) and klotho ablated mice, which led to identification of klotho as an Fgf23 signaling cofactor. Here, we generated Fgf23 and klotho double-knockout (Fgf23(-/-)/klotho(-/-)) mice to test the hypothesis whether Fgf23 has a klotho-independent function. Fgf23(-/-)/klotho(-/-) mice are viable and have high serum phosphate levels, similar to Fgf23(-/-) and klotho(-/-) single-knockout mice. In addition, the Fgf23(-/-)/klotho(-/-) mice have increased renal expression of the sodium/phosphate cotransporter NaP(i)2a and of 1- alpha-hydroxylase concomitant with increased serum levels of 1,25-dihydroxyvitamin-D, as also observed in the Fgf23(-/-) and klotho(-/-) mice. Moreover, Fgf23(-/-)/klotho(-/-) mice show soft tissue and vascular calcification, severe muscle wasting, hypogonadism, pulmonary emphysema, distention of intestinal wall, and skin atrophy, all of which are also seen in Fgf23(-/-) and klotho(-/-) mice. Notably, injection of bioactive FGF23 protein into Fgf23(-/-)/klotho(-/-) and klotho(-/-) mice does not lower serum phosphate, whereas in wild-type and Fgf23(-/-) mice, it reduces serum phosphate. Together, these results provide compelling evidence that Fgf23 does not have a klotho-independent role in the regulation of systemic phosphate and vitamin D homeostasis.
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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.