Document Detail


Klotho in health and disease.
MedLine Citation:
PMID:  22660551     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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:
Makoto Kuro-o
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; Review    
Journal Detail:
Title:  Current opinion in nephrology and hypertension     Volume:  21     ISSN:  1473-6543     ISO Abbreviation:  Curr. Opin. Nephrol. Hypertens.     Publication Date:  2012 Jul 
Date Detail:
Created Date:  2012-06-04     Completed Date:  2012-10-03     Revised Date:  2013-05-02    
Medline Journal Info:
Nlm Unique ID:  9303753     Medline TA:  Curr Opin Nephrol Hypertens     Country:  England    
Other Details:
Languages:  eng     Pagination:  362-8     Citation Subset:  IM    
Affiliation:
Department of Pathology, The University of Texas Southwestern Medical Center at Dallas, Dallas, Texas 75390-9072, USA. Makoto.Kuro-o@UTSouthwestern.edu
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
Descriptor/Qualifier:
Acute Kidney Injury / metabolism
Animals
Chronic Disease
Fibroblast Growth Factors / metabolism
Glucuronidase / genetics,  metabolism*
Homeostasis
Humans
Kidney / metabolism*,  pathology,  physiopathology
Kidney Diseases / genetics,  metabolism*,  pathology,  physiopathology
Neoplasms / genetics,  metabolism*,  pathology
Phosphates / metabolism
Signal Transduction*
Grant Support
ID/Acronym/Agency:
R01AG19712/AG/NIA NIH HHS; R01DK091392/DK/NIDDK NIH HHS
Chemical
Reg. No./Substance:
0/Phosphates; 0/fibroblast growth factor 23; 62031-54-3/Fibroblast Growth Factors; EC 3.2.1.31/Glucuronidase; EC 3.2.1.31/klotho protein

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


Previous Document:  Calcium-sensing receptor gene polymorphisms in patients with calcium nephrolithiasis.
Next Document:  Targeting signaling pathways in glomerular diseases.