The FGF23/KLOTHO Regulatory Network and Its Roles in Human Disorders.

Abstract

The functions of Klotho (KL) are multifaceted and include the regulation of aging and mineral metabolism. It was originally identified as the gene responsible for premature aging-like symptoms in mice and was subsequently shown to function as a coreceptor in the fibroblast growth factor (FGF) 23 signaling pathway. The discovery of KL as a partner for FGF23 led to significant advances in understanding of the molecular mechanisms underlying phosphate and vitamin D metabolism, and simultaneously clarified the pathogenic roles of the FGF23 signaling pathway in human diseases. These novel insights led to the development of new strategies to combat disorders associated with the dysregulated metabolism of phosphate and vitamin D, and clinical trials on the blockade of FGF23 signaling in X-linked hypophosphatemic rickets are ongoing. Molecular and functional insights on KL and FGF23 have been discussed in this review and were extended to how dysregulation of the FGF23/KL axis causes human disorders associated with abnormal mineral metabolism.

• Authors: S Kinoshita, M Kawai
• Journal: Vitamins and hormones (Vitam Horm) Vol. 101 Pg. 151-74 ( 2016) ISSN: 0083-6729 [Print] United States
• PMID: 27125741 (Publication Type: Journal Article, Review)
• Copyright: © 2016 Elsevier Inc. All rights reserved.

Chemical References

• FGF23 protein, human
• Fgf23 protein, mouse
• Minerals
• Phosphates
• Receptors, Fibroblast Growth Factor
• Vitamin D
• Fibroblast Growth Factors
• Fibroblast Growth Factor-23
• Glucuronidase
• Klotho Proteins
• Calcium

Topics

• Animals
• Calcium (metabolism)
• Fibroblast Growth Factor-23
• Fibroblast Growth Factors (chemistry, genetics, physiology)
• Gene Expression
• Glucuronidase (genetics, physiology)
• Homeostasis (physiology)
• Humans
• Klotho Proteins
• Metabolic Diseases
• Minerals (metabolism)
• Mutation
• Phosphates (metabolism)
• Receptors, Fibroblast Growth Factor
• Renal Insufficiency, Chronic
• Signal Transduction
• Vitamin D (metabolism)