| Authors |
Bansal S, Friedrichs WE, Velagapudi C, Feliers D, Khazim K, Horn D, Cornell JE,
Werner SL, Fanti P
|
| Submitted By |
Shweta Bansal on 1/16/2018 |
| Status |
Published |
| Journal |
Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association |
| Year |
2017 |
| Date Published |
6/1/2017 |
| Volume : Pages |
32 : 960 - 968 |
| PubMed Reference |
|
| Abstract |
Circulating levels of fibroblast growth factor 23 (FGF23) increase progressively
and correlate with systemic inflammation in chronic kidney disease (CKD). The
aim of this study was to identify and characterize the causal relationship
between FGF23 and inflammation in CKD., Circulating FGF23 and inflammatory
cytokines were correlated in healthy subjects and patients with varying levels
of CKD. In addition, FGF23 expression in blood and solid organs was measured in
normal mice that were exposed acutely (one time) or chronically (2-week) to
low-dose lipopolysaccharide (LPS); chronic exposure being either sustained
(subcutaneous pellets), intermittent (daily injections) or combined sustained
plus acute (subcutaneous pellets plus acute injection on the day of sacrifice).
Blood was analyzed for both terminal (cFGF23) and intact (iFGF23) FGF23 levels.
Solid tissues were investigated with immunohistochemistry, enzyme-linked
immunosorbent assay and reverse transcription polymerase chain reaction., FGF23
levels correlated significantly with neutrophil gelatinase-associated lipocalin
( r = 0.72, P < 0.001), C-reactive protein ( r = 0.38, P < 0.001), tumor
necrosis factor-a ( r = 0.32, P = 0.001) and interleukin-6 ( r = 0.48, P <
0.001). Acute LPS administration increased tissue FGF23 mRNA and plasma levels
of cFGF23 but not iFGF23. Neither chronic sustained nor chronic pulsatile LPS
increased the tissue or circulating levels of FGF23. However, acute on chronic
LPS raised tissue FGF23 mRNA and both circulating cFG23 and iFGF23.
Interestingly, the spleen was the major source of FGF23., Acute on chronic
exposure to LPS stimulates FGF23 production in a normal mouse model of
inflammation. We provide the first evidence that the spleen, under these
conditions, contributes substantially to elevated circulating FGF23 levels.
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