Abstract
In comparison to the regulation of calcium homeostasis, which has been widely studied over the last several decades, phosphate homeostasis is little understood. The parathyroid hormone (PTH)/vitamin D axis has traditionally been used as a conceptual framework for understanding mineral metabolism. Recently, the fundamental regulator of phosphate homeostasis, fibroblast growth factor 23 (FGF23), which is produced by osteocytes and is involved in the hormonal bone-parathyroid-kidney axis, has attracted more attention. The secretion of FGF23 is controlled by diet, serum phosphate levels, PTH, and 1,25(OH)2 vitamin D. FGF-23, the FGF receptors and the obligate co-receptor α-Klotho work in concert to affect FGF-23 actions on targeted organs. Despite all efforts to investigate pleotropic effects of FGF23 in various endocrine organs, many aspects of the regulation and functions of FGF23 and the exact crosstalk among FGF23, serum phosphate, calcium, PTH, and vitamin D in the regulation of mineral homeostasis remain unclear; much efforts need to be established before it can be moved toward therapeutic applications. In this regard, we provide a brief overview of the novel findings in the regulation and function of FGF23 and refer to related questions and hypotheses not answered yet, which can be a window for future projects. We also focus on the current knowledge about the role of FGF23 obtained from our researches in recent years.
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Abbreviations
- FGF23:
-
Fibroblast growth factor 23
- FGFR:
-
Fibroblast growth factor receptor
- PTH:
-
Parathyroid hormone
- 1,25-vit D:
-
1,25-Dihydroxy vitamin D3
- ADHR:
-
Autosomal dominant hypophosphatemic rickets
- TIO:
-
Tumor induced-osteomalacia
- CKD:
-
Chronic kidney disease
- ADAM17:
-
Metaloproteinase
- ROMK1:
-
Renal outer medullary potassium channel
- Npt2a/c:
-
Na+‐phosphate cotransporters
- TRPV5:
-
Transient receptor potential cation channel subfamily V member 5
- TRPC6:
-
Transient receptor potential cation channel subfamily C member
- NF-ҡβ:
-
Nuclear factor kappa-light-chain-enhancer of activated B cells
- p38MAPK:
-
Serine/threonine kinase p38 mitogen-activated protein kinase
- PKC:
-
Serine/threonine kinase protein kinase C
- LPS:
-
Lipopolysaccharide
- IL-1β:
-
Interleukin 1β
- TNFα:
-
Tumor necrosis factor alpha
- TWEAK:
-
The tumor necrosis factor like weak inducer of apoptosis
- PAI-1:
-
Plasminogen activator inhibitor-1
- PLCγ1:
-
Phospholipase Cγ1
- NFAT:
-
Nuclear factor that activates T cells
- GD:
-
Graves’ disease
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Acknowledgements
We dedicate this article to Prof. Gholam Hossein Ranjbar Omrani, who passed away recently and had the leading role in all steps of this project. He was a pioneer and a world-class scientist in endocrine and metabolism researches. We tried to gather all his novel findings in the topic of FGF23 for a bit of appreciation for their tireless efforts in training junior researchers for many years. Hereby, the authors would like to thank Dr. Manica Negahdaripour for English editing of the manuscript.
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SD: did complete searching to gather all related papers, and prepared the first draft of the manuscript, FK: prepared the second draft of the manuscript, AA: made the initial plan of the project, read the second draft, and revised article, FS: made the final plan for the project, did a final proof of manuscript, and the was the corresponding author; MS: made the initial plan of the project, and revised the final draft of manuscript and the correspondence. All authors have read and agreed to the published version of the manuscript.
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Dastghaib, S., Koohpeyma, F., Shams, M. et al. New concepts in regulation and function of the FGF23. Clin Exp Med 23, 1055–1066 (2023). https://doi.org/10.1007/s10238-022-00844-x
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DOI: https://doi.org/10.1007/s10238-022-00844-x