Journal
ANNUAL REVIEW OF PHYSIOLOGY, VOL 75
Volume 75, Issue -, Pages 503-533Publisher
ANNUAL REVIEWS
DOI: 10.1146/annurev-physiol-030212-183727
Keywords
calcium; phosphate; FGF23; Klotho; kidney; bone
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Funding
- NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES [R01DK092461, R01DK091392] Funding Source: NIH RePORTER
- NIDDK NIH HHS [R01 DK091392, R01 DK092461] Funding Source: Medline
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The metabolically active and perpetually remodeling calcium phosphate-based endoskeleton in terrestrial vertebrates sets the demands on whole-organism calcium and phosphate homeostasis that involves multiple organs in terms of mineral flux and endocrine cross talk. The fibroblast growth factor (FGF)-Klotho endocrine networks epitomize the complexity of systems biology, and specifically, the FGF23-alpha Klotho axis highlights the concept of the skeleton holding the master switch of homeostasis rather than a passive target organ as hitherto conceived. Other than serving as a coreceptor for FGF23, alpha Klotho circulates as an endocrine substance with a multitude of effects. This review covers recent data on the physiological regulation and function of the complex FGF23-alpha Klotho network. Chronic kidney disease is a common pathophysiological state in which FGF23-alpha Klotho, a multiorgan endocrine network, is deranged in a self-amplifying vortex resulting in organ dysfunction of the utmost severity that contributes to its morbidity and mortality.
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