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Novel functions of circulating Klotho
Julia M Hum1, Linda O'Bryan2, Rosamund C Smith2
1Department of Medical and Molecular Genetics, Division of Molecular Genetics and Gene Therapy, Indiana University School of Medicine, Indianapolis, IN 46202, USA; Division of Biomedical Science, Marian University School of Osteopathic Medicine, Indianapolis, IN 46222, USA.
Insights
Studies on rare mineral metabolism diseases reveal αKlotho (αKL) and FGF23 functions. Extended delivery of cleaved αKlotho (cKL) in mouse models shows promise for treating chronic kidney disease-mineral bone disorder (CKD-MBD).
Area of Science:
- Mineral metabolism
- Endocrinology
- Nephrology
Background:
- Rare diseases of mineral metabolism have elucidated key biological functions of αKlotho (αKL) and Fibroblast growth factor-23 (FGF23).
- These insights have significant implications for prevalent conditions like chronic kidney disease-mineral bone disorder (CKD-MBD).
- αKL primarily regulates mineral homeostasis in the kidney as a co-receptor for FGF23.
Purpose of the Study:
- To review recent findings on the role of cleaved αKlotho (cKL) as a circulating factor.
- To examine the effects of extended cKL delivery in mouse models mimicking CKD-MBD phenotypes.
Main Methods:
- Review of studies involving extended delivery of cleaved αKlotho (cKL).
- Utilized mouse models exhibiting phenotypes relevant to CKD-MBD.
Main Results:
- Emerging data highlight αKL's function beyond its co-receptor role, acting as a cleaved circulating factor (cKL).
- Extended cKL delivery in mouse models demonstrated therapeutic potential for CKD-MBD related phenotypes.
Conclusions:
- Cleaved αKlotho (cKL) represents a potential therapeutic avenue for CKD-MBD.
- Further research into cKL's biological functions and therapeutic applications is warranted.
Abstract:
A significant portion of the key biological functions of αKlotho (αKL) and its cognate ligand Fibroblast growth factor-23 (FGF23) have been revealed through the study of rare diseases of mineral metabolism. These findings have far reaching implications for common disorders such as chronic kidney disease-mineral bone disorder (CKD-MBD). αKL's predominant effect on mineral homeostasis is through its actions in the kidney as a co-receptor for FGF23, however emerging data has shed light on its capacity to act as a circulating factor through the cleavage of the transmembrane form of αKL ('mKL') to produce 'cleaved KL' or 'cKL'. This review summarizes new findings from studies using extended delivery of cKL to mouse models with phenotypes reflecting those arising in CKD-MBD.
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