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Klotho in health and disease.
Curr Opin Nephrol Hypertens. 2012 Jul; 21(4):362-8.CO

Abstract

PURPOSE OF REVIEW

The klotho gene was originally identified as a putative aging-suppressor gene in mice that extended life span when overexpressed and induced a premature aging syndrome when disrupted. Subsequently, it became clear that the Klotho family of membrane proteins function as obligate co-receptors for endocrine fibroblast growth factors (FGFs) that regulate various metabolic processes. This review focuses on the Klotho-FGF23 endocrine system that maintains phosphate (Pi) homeostasis, and discusses the mechanism of action and the potential contribution of Klotho deficiency to acute kidney injury (AKI), chronic kidney disease (CKD) and cancer.

RECENT FINDINGS

Klotho functions as a receptor for the phosphaturic hormone FGF23. Klotho deficiency induces resistance to FGF23 and predisposition to Pi retention, which represents a critical feature of pathophysiology of CKD. The extracellular domain of Klotho protein is subject to ectodomain shedding and released into the blood and urine. Secreted Klotho functions as a humoral factor that inhibits AKI, vascular calcification, renal fibrosis, and cancer metastasis in an FGF23-independent manner.

SUMMARY

Various factors that affect Klotho expression have been identified. Prevention of Klotho decline and supplementation of Klotho can be a novel therapeutic strategy for many age-related diseases.

Authors+Show Affiliations

Department of Pathology, The University of Texas Southwestern Medical Center at Dallas, Dallas, Texas 75390-9072, USA. Makoto.Kuro-o@UTSouthwestern.edu

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Review

Language

eng

PubMed ID

22660551

Citation

Kuro-o, Makoto. "Klotho in Health and Disease." Current Opinion in Nephrology and Hypertension, vol. 21, no. 4, 2012, pp. 362-8.
Kuro-o M. Klotho in health and disease. Curr Opin Nephrol Hypertens. 2012;21(4):362-8.
Kuro-o, M. (2012). Klotho in health and disease. Current Opinion in Nephrology and Hypertension, 21(4), 362-8. https://doi.org/10.1097/MNH.0b013e32835422ad
Kuro-o M. Klotho in Health and Disease. Curr Opin Nephrol Hypertens. 2012;21(4):362-8. PubMed PMID: 22660551.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Klotho in health and disease. A1 - Kuro-o,Makoto, PY - 2012/6/5/entrez PY - 2012/6/5/pubmed PY - 2012/10/4/medline SP - 362 EP - 8 JF - Current opinion in nephrology and hypertension JO - Curr Opin Nephrol Hypertens VL - 21 IS - 4 N2 - PURPOSE OF REVIEW: The klotho gene was originally identified as a putative aging-suppressor gene in mice that extended life span when overexpressed and induced a premature aging syndrome when disrupted. Subsequently, it became clear that the Klotho family of membrane proteins function as obligate co-receptors for endocrine fibroblast growth factors (FGFs) that regulate various metabolic processes. This review focuses on the Klotho-FGF23 endocrine system that maintains phosphate (Pi) homeostasis, and discusses the mechanism of action and the potential contribution of Klotho deficiency to acute kidney injury (AKI), chronic kidney disease (CKD) and cancer. RECENT FINDINGS: Klotho functions as a receptor for the phosphaturic hormone FGF23. Klotho deficiency induces resistance to FGF23 and predisposition to Pi retention, which represents a critical feature of pathophysiology of CKD. The extracellular domain of Klotho protein is subject to ectodomain shedding and released into the blood and urine. Secreted Klotho functions as a humoral factor that inhibits AKI, vascular calcification, renal fibrosis, and cancer metastasis in an FGF23-independent manner. SUMMARY: Various factors that affect Klotho expression have been identified. Prevention of Klotho decline and supplementation of Klotho can be a novel therapeutic strategy for many age-related diseases. SN - 1473-6543 UR - https://www.unboundmedicine.com/medline/citation/22660551/Klotho_in_health_and_disease_ L2 - https://doi.org/10.1097/MNH.0b013e32835422ad DB - PRIME DP - Unbound Medicine ER -