FGF-23 inhibits renal tubular phosphate transport and is a PHEX substrate - PubMed (original) (raw)
. 2001 Jun 22;284(4):977-81.
doi: 10.1006/bbrc.2001.5084.
Affiliations
- PMID: 11409890
- DOI: 10.1006/bbrc.2001.5084
FGF-23 inhibits renal tubular phosphate transport and is a PHEX substrate
A E Bowe et al. Biochem Biophys Res Commun. 2001.
Abstract
Oncogenic osteomalacia (OOM), X-linked hypophosphatemia (XLH), and autosomal dominant hypophosphatemic rickets (ADHR) are phenotypically similar disorders characterized by hypophosphatemia, decreased renal phosphate reabsorption, normal or low serum calcitriol concentrations, normal serum concentrations of calcium and parathyroid hormone, and defective skeletal mineralization. XLH results from mutations in the PHEX gene, encoding a membrane-bound endopeptidase, whereas ADHR is associated with mutations of the gene encoding FGF-23. Recent evidence that FGF-23 is expressed in mesenchymal tumors associated with OOM suggests that FGF-23 is responsible for the phosphaturic activity previously termed "phosphatonin." Here we show that both wild-type FGF-23 and the ADHR mutant, FGF-23(R179Q), inhibit phosphate uptake in renal epithelial cells. We further show that the endopeptidase, PHEX, degrades native FGF-23 but not the mutant form. Our results suggest that FGF-23 is involved in the pathogenesis of these three hypophosphatemic disorders and directly link PHEX and FGF-23 within the same biochemical pathway.
Copyright 2001 Academic Press.
Similar articles
- Homozygous ablation of fibroblast growth factor-23 results in hyperphosphatemia and impaired skeletogenesis, and reverses hypophosphatemia in Phex-deficient mice.
Sitara D, Razzaque MS, Hesse M, Yoganathan S, Taguchi T, Erben RG, Jüppner H, Lanske B. Sitara D, et al. Matrix Biol. 2004 Nov;23(7):421-32. doi: 10.1016/j.matbio.2004.09.007. Matrix Biol. 2004. PMID: 15579309 Free PMC article. - FGF23, PHEX, and MEPE regulation of phosphate homeostasis and skeletal mineralization.
Quarles LD. Quarles LD. Am J Physiol Endocrinol Metab. 2003 Jul;285(1):E1-9. doi: 10.1152/ajpendo.00016.2003. Am J Physiol Endocrinol Metab. 2003. PMID: 12791601 Review. - Fibroblast growth factor-23 is the phosphaturic factor in tumor-induced osteomalacia and may be phosphatonin.
Fukumoto S, Yamashita T. Fukumoto S, et al. Curr Opin Nephrol Hypertens. 2002 Jul;11(4):385-9. doi: 10.1097/00041552-200207000-00003. Curr Opin Nephrol Hypertens. 2002. PMID: 12105387 Review. - The wrickkened pathways of FGF23, MEPE and PHEX.
Rowe PS. Rowe PS. Crit Rev Oral Biol Med. 2004 Sep 1;15(5):264-81. doi: 10.1177/154411130401500503. Crit Rev Oral Biol Med. 2004. PMID: 15470265 Free PMC article. Review.
Cited by
- The Relationship between Sclerostin and Kidney Transplantation Mineral Bone Disorders: A Molecule of Controversies.
Afsar B, Afsar RE, Caliskan Y, Lentine KL. Afsar B, et al. Calcif Tissue Int. 2024 Oct;115(4):339-361. doi: 10.1007/s00223-024-01261-w. Epub 2024 Jul 30. Calcif Tissue Int. 2024. PMID: 39078512 Free PMC article. Review. - MiR-539-3p impairs osteogenesis by suppressing Wnt interaction with LRP-6 co-receptor and subsequent inhibition of Akap-3 signaling pathway.
Tripathi A, John AA, Kumar D, Kaushal SK, Singh DP, Husain N, Sarkar J, Singh D. Tripathi A, et al. Front Endocrinol (Lausanne). 2022 Sep 29;13:977347. doi: 10.3389/fendo.2022.977347. eCollection 2022. Front Endocrinol (Lausanne). 2022. PMID: 36267566 Free PMC article. - PHEXL222P Mutation Increases Phex Expression in a New ENU Mouse Model for XLH Disease.
El Hakam C, Parenté A, Baraige F, Magnol L, Forestier L, Di Meo F, Blanquet V. El Hakam C, et al. Genes (Basel). 2022 Jul 28;13(8):1356. doi: 10.3390/genes13081356. Genes (Basel). 2022. PMID: 36011266 Free PMC article. - A Novel Synonymous Variant of PHEX in a Patient with X-Linked Hypophosphatemia.
Ma X, Pang Q, Zhang Q, Jiang Y, Wang O, Li M, Xing X, Xia W. Ma X, et al. Calcif Tissue Int. 2022 Dec;111(6):634-640. doi: 10.1007/s00223-022-01003-w. Epub 2022 Jul 14. Calcif Tissue Int. 2022. PMID: 35831717 - Identification of a Novel Missense Mutation of the PHEX Gene in a Large Chinese Family with X-Linked Hypophosphataemia.
Yang Y, Wang Y, Shen Y, Liu M, Dai S, Wang X, Liu H. Yang Y, et al. Front Genet. 2022 Feb 17;13:792183. doi: 10.3389/fgene.2022.792183. eCollection 2022. Front Genet. 2022. PMID: 35251124 Free PMC article.
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Other Literature Sources
Molecular Biology Databases