Introduction Fibroblast growth factor 23 (FGF23) is a major regulator of
phosphate and vitamin D metabolism in the kidney, and its higher levels in
plasma are associated with poorer outcomes in kidney and cardiovascular
diseases. It is produced by bone cells upon enhanced oxidative stress and
inhibits renal phosphate reabsorption and calcitriol (active form of vitamin D)
production. Bilirubin, the final product of the heme catabolic pathway in the
vascular bed, has versatile biological functions, including antioxidant and
anti-inflammatory effects. This study explored whether bilirubin alters FGF23
production.
Methods Experiments were performed using UMR106 osteoblast-like cells.
Fgf23 transcript levels were determined by quantitative real-time
polymerase chain reaction, C-terminal and intact FGF23 protein levels were
determined by enzyme-linked immunosorbent assay, and cellular oxidative stress
was assessed by CellROX assay.
Results Unconjugated bilirubin down-regulated Fgf23 gene
transcription and FGF23 protein abundance; these effects were paralleled by
lower cellular oxidative stress levels. Also, conjugated bilirubin reduced
Fgf23 mRNA abundance.
Conclusion Bilirubin down-regulates FGF23 production in UMR106 cells, an
effect likely to be dependent on the reduction of cellular oxidative stress.