Coupling fibroblast growth factor 23 production and cleavage: iron deficiency, rickets, and kidney disease

If you need an accessible version of this item, please submit a remediation request.
Date
2014-07
Language
American English
Embargo Lift Date
Committee Members
Degree
Degree Year
Department
Grantor
Journal Title
Journal ISSN
Volume Title
Found At
Ovid Technologies (Wolters Kluwer) - Lippincott Williams & Wilkins
Abstract

PURPOSE OF REVIEW: High levels of fibroblast growth factor 23 (FGF23) cause the rare disorders of hypophosphatemic rickets and are a risk factor for cardiovascular disease and death in patients with chronic kidney disease (CKD). Despite major advances in understanding FGF23 biology, fundamental aspects of FGF23 regulation in health and in CKD remain mostly unknown. RECENT FINDINGS: Autosomal dominant hypophosphatemic rickets (ADHR) is caused by gain-of-function mutations in FGF23 that prevent its proteolytic cleavage, but affected individuals experience a waxing and waning course of phosphate wasting. This led to the discovery that iron deficiency is an environmental trigger that stimulates FGF23 expression and hypophosphatemia in ADHR. Unlike osteocytes in ADHR, normal osteocytes couple increased FGF23 production with commensurately increased FGF23 cleavage to ensure that normal phosphate homeostasis is maintained in the event of iron deficiency. Simultaneous measurement of FGF23 by intact and C-terminal assays supported these breakthroughs by providing minimally invasive insight into FGF23 production and cleavage in bone. These findings also suggest a novel mechanism of FGF23 elevation in patients with CKD, who are often iron deficient and demonstrate increased FGF23 production and decreased FGF23 cleavage, consistent with an acquired state that mimics the molecular pathophysiology of ADHR. SUMMARY: Iron deficiency stimulates FGF23 production, but normal osteocytes couple increased FGF23 production with increased cleavage to maintain normal circulating levels of biologically active hormone. These findings uncover a second level of FGF23 regulation within osteocytes, failure of which culminates in elevated levels of biologically active FGF23 in ADHR and perhaps CKD.

Description
item.page.description.tableofcontents
item.page.relation.haspart
Cite As
Wolf, M., & White, K. E. (2014). Coupling FGF23 Production and Cleavage: Iron Deficiency, Rickets and Kidney Disease. Current Opinion in Nephrology and Hypertension, 23(4), 411–419. http://doi.org/10.1097/01.mnh.0000447020.74593.6f
ISSN
1473-6543
Publisher
Series/Report
Sponsorship
Major
Extent
Identifier
Relation
Journal
Current Opinion in Nephrology and Hypertension
Source
PMC
Alternative Title
Type
Article
Number
Volume
Conference Dates
Conference Host
Conference Location
Conference Name
Conference Panel
Conference Secretariat Location
Version
Author's manuscript
Full Text Available at
This item is under embargo {{howLong}}