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FGF23-αKlotho as a paradigm for a kidney-bone network
1Center for Molecular Medicine, Jichi Medical University, Tochigi, Japan; Department of Pathology, University of Texas Southwestern Medical Center, Dallas, TX, USA; Charles and Jane Pak Center of Mineral Metabolism and Clinical Research, University of Texas Southwestern Medical Center, Dallas, TX, USA.
Bone
|November 17, 2016
Summary
The vertebrate endoskeleton is a vital organ regulating mineral and energy metabolism. Fibroblast growth factors (FGFs) and Klotho proteins are key players, with disruptions causing significant health issues, especially in chronic kidney disease (CKD).
Area of Science:
- Endocrinology
- Mineral Metabolism
- Skeletal Physiology
Background:
- The vertebrate endoskeleton functions as a major organ involved in mineral and energy metabolism, not just locomotion.
- Mineral balance is maintained through complex endocrine signaling networks involving the intestine, kidney, and bone.
- Fibroblast growth factors (FGFs) and Klotho gene families are integral to skeletal and mineral homeostasis.
Purpose of the Study:
- To elucidate the roles of FGF23 and αKlotho in mineral metabolism.
- To investigate the upstream regulation and downstream functions of FGF23 and αKlotho.
- To understand the impact of genetic lesions and acquired conditions on mineral metabolism networks.
Main Methods:
- Review of endocrine signaling pathways.
- Analysis of genetic lesions affecting mineral metabolism.
- Examination of acquired conditions like chronic kidney disease (CKD).
Main Results:
- FGF23 (primarily from bone) and αKlotho (primarily from kidney) are critical for mineral metabolism, with diverse and incompletely understood roles.
- Genetic defects in this network cause various mineral metabolism disturbances.
- Chronic kidney disease is associated with extreme FGF23 elevation and αKlotho suppression, leading to widespread organ dysfunction.
Conclusions:
- Disorders of mineral metabolism, particularly involving phosphate, FGF23, and αKlotho, are central to the pathophysiology and complications of CKD.
- Understanding these derangements is crucial for managing CKD progression and extra-renal complications.
- Further research into FGF23 and αKlotho regulation and function is needed.
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