Does Fgf23-klotho activity influence vascular and soft tissue calcification through regulating mineral ion metabolism?
Recent studies describe a novel role of fibroblast growth factor-23 (Fgf23)-klotho activity in the systemic regulation of calcium and phosphate homeostasis. Both Fgf23 and klotho ablated mice develop extensive vascular and soft tissue calcification. Inability to clear the required amount of phosphate by the kidney, due to the absence of Fgf23-klotho activity, leads to increased accumulation of serum phosphate in these genetically modified mice, causing extensive calcification. Serum calcium and 1,25 hydroxyvitamin D levels are also elevated in both Fgf23 and klotho ablated mice. Moreover, increased sodium phosphate co-transporter activity in both Fgf23 and klotho ablated mice increases renal phosphate reabsorption which in turn can facilitate calcification. Collectively, these observations bring new insights into our understanding of the roles of the Fgf23-klotho axis in the development of vascular and soft tissue calcification.
Department of Developmental Biology, Harvard School of Dental Medicine, Boston, Massachusetts, USA.
Fahad
F
Memon
Mohga
M
El-Abbadi
Teruyo
T
Nakatani
Takashi
T
Taguchi
Beate
B
Lanske
M Shawkat
MS
Razzaque
D000818:Animals; D001808:Blood Vessels / Q000378:metabolism / Q000473:pathology; D002114:Calcinosis / Q000209:etiology* / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control; D003238:Connective Tissue / Q000378:metabolism / Q000473:pathology; D000089703:Fibroblast Growth Factor-23; D005346:Fibroblast Growth Factors / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D005966:Glucuronidase / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D006801:Humans; D000090265:Klotho Proteins; D051379:Mice; D018345:Mice, Knockout; D008903:Minerals / Q000378:metabolism; D009154:Mutation; D010710:Phosphates / Q000378:metabolism; D015398:Signal Transduction; D050613:Sodium-Phosphate Cotransporter Proteins, Type IIa / Q000378:metabolism
C000717427:FGF23 protein, human; C000717428:Fgf23 protein, mouse; D008903:Minerals; D010710:Phosphates; D050613:Sodium-Phosphate Cotransporter Proteins, Type IIa; D005346:Fibroblast Growth Factors; D000089703:Fibroblast Growth Factor-23; D005966:Glucuronidase; D000090265:Klotho Proteins