ArticleScientific reports2018
Central role of the proximal tubular αKlotho/FGF receptor complex in FGF23-regulated phosphate and vitamin D metabolism.
Article in Scientific reports, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers, 1 of them a synthesis that pooled it.
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Who cites it
21 citing papers in PubMed, 1 synthesis or guideline pooled it, 35 citations in OpenAlex.
- Meta-Analysis of the Association between Fibroblast Growth Factor 23 and Mortality and Cardiovascular Events in Hemodialysis Patients.Blood purification · 2019Pooled it
- Klotho revisited: tubular heterogeneity reshapes mineral metabolism, aging, and CKD.Pflugers Archiv : European journal of physiology · 2026Review
- Klotho in the kidney distal convolution regulates urinary Klotho excretion and kidney calcium reabsorption, but not phosphate homeostasis.Kidney international · 2026Article
- [Potential of early diagnosis and targeted therapy for Klotho protein in chronic kidney disease].Zhong nan da xue xue bao. Yi xue ban = Journal of Central South University. Medical sciences · 2025Review
- Partial renal deletion of Klotho is not sufficient to impact renal electrolyte handling in distal convoluted tubule specific knock-out mice.Physiological reports · 2025Article
- Sexually dimorphic renal expression of mouse Klotho is directed by a kidney-specific distal enhancer responsive to HNF1b.Communications biology · 2024Article
- Fibroblast growth factor 23-mediated regulation of osteoporosis: Assessed via Mendelian randomization and in vitro study.Journal of cellular and molecular medicine · 2024Article
- Sexually dimorphic renal expression ofResearch square · 2024Article
- Management of Fibroblast Growth Factor Inhibitor Treatment-emergent Adverse Events of Interest in Patients with Locally Advanced or Metastatic Urothelial Carcinoma.European urology open science · 2023Article
- Possible contribution of phosphate to the pathogenesis of chronic kidney disease in dolphins.Scientific reports · 2023Article
- Regulation of FGF23 production and phosphate metabolism by bone-kidney interactions.Nature reviews. Nephrology · 2023Review
- Phosphate Dysregulation and Metabolic Syndrome.Nutrients · 2022Article
- Fibroblast Growth Factor 23 and Osteoporosis: Evidence from Bench to Bedside.International journal of molecular sciences · 2022Review
- Pathobiology of the Klotho Antiaging Protein and Therapeutic Considerations.Frontiers in aging · 2022Review
- FGF23 and Vitamin D Metabolism.JBMR plus · 2021Article
- Targeting fibroblast growth factor 23-responsive pathways uncovers controlling genes in kidney mineral metabolism.Kidney international · 2021Article
- FGF23 signalling and physiology.Journal of molecular endocrinology · 2021Review
- Serum Klotho in Living Kidney Donors and Kidney Transplant Recipients: A Meta-Analysis.Journal of clinical medicine · 2020Article
- Osteocytic FGF23 and Its Kidney Function.Frontiers in endocrinology · 2020Review
- FGF23 Synthesis and Activity.Current molecular biology reports · 2019Article
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Fibroblast growth factor 23 (FGF23) plays critical roles in phosphate handling and vitamin D metabolism in the kidney. However, the effector cells of FGF23 in the kidney remain unclear. αKlotho, a putative enzyme possessing β-glucuronidase activity and also a permissive co-receptor for FGF23 to bind to FGF receptors (FGFRs), is expressed most abundantly in distal convoluted tubules, whereas it is expressed modestly in proximal tubules. Key molecular players of phosphate homeostasis and vitamin D-metabolizing enzymes are known to localize in proximal tubules. To clarify the direct function of FGF23 on proximal tubules, we ablated αKlotho or Fgfr1-4 genes specifically from these tubules using the Cre-loxP-mediated genetic recombination. Both conditional knockout mouse lines showed similar phenotypes that resembled those of systemic αKlotho or Fgf23 knockout mice. Compared with control mice, they showed significantly elevated levels of plasma phosphate, FGF23 and 1,25-dihydroxyvitamin D, ectopic calcification in the kidney and aging-related phenotypes like growth retardation, osteoporosis and shortened lifespan. These findings suggest that the primary function of FGF23 on mineral metabolism is mediated through αKlotho/FGFR co-receptors expressed in proximal tubular cells, and that the putative enzymatic function of αKlotho in the proximal tubule has a minor role in systemic mineral metabolism.
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