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Cited by 587Parathyroid Disorders and TreatmentsAlkaline Phosphatase Research StudiesRenal function and acid-base balance

Fibroblast Growth Factor 23 and Klotho: Physiology and Pathophysiology of an Endocrine Network of Mineral Metabolism

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Hu, Ming Chang, Shiizaki, Kazuhiro, Kuro-o, Makoto, Moe, Orson W.·2013·Annual Review of Physiology
DOI 10.1146/annurev-physiol-030212-183727PMC PMC3770142
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Abstract

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-αKlotho 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, αKlotho 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-αKlotho network. Chronic kidney disease is a common pathophysiological state in which FGF23-αKlotho, 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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Cited by

Sorted by citations

Authors
Hu, M. C., Shiizaki, K., Kuro-o, M., & Moe, O. W.
Affiliations
  • The University of Texas Southwestern Medical Center (US)
  • Pathology, and
ORCID
Venue
Annual Review of Physiology
Publisher
Annual Reviews
Published
2013-02-10
Volume
75
Issue
1
Pages
503-533
ISSN
  • 0066-4278 (ISSN-L)
  • 1545-1585
DOI
10.1146/annurev-physiol-030212-183727
PMC
PMC3770142
OpenAlex
W2110023205
Cited by
587
References
14
Citations by year
2026: 21 · 2025: 30 · 2024: 39 · 2023: 43 · 2022: 50 · 2021: 60 · 2020: 37 · 2019: 57 · 2018: 60 · 2017: 38 · 2016: 44 · 2015: 44 · 2014: 47 · 2013: 17
FWCI
6.64
Type
journal article
Language
en
Open access
Locations
  • Annual Review of Physiology (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • National Institutes of Health
  • National Institute of Diabetes and Digestive and Kidney Diseases (R01DK091392, R01DK092461)
Topics
  • Health Sciences › Medicine › Nephrology › Parathyroid Disorders and Treatments
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Alkaline Phosphatase Research Studies
  • Health Sciences › Medicine › Nephrology › Renal function and acid-base balance
Keywords
fibroblast growth factor 23, Klotho, alpha-klotho, mineral metabolism, calcium homeostasis, phosphate homeostasis, chronic kidney disease, endoskeleton
MeSH terms
Fibroblast Growth Factor-23, Klotho Proteins, Animals, Bone and Bones, Endocrine System, Fibroblast Growth Factors, Glucuronidase, Homeostasis, Humans, Intestines, Kidney, Minerals

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