English (United Kingdom)

https://curated-unify.zendy.io/wp-json/zendy-region/v1/featured_content/oa?rat=en

https://curated-unify.zendy.io/wp-json/zendy-region/v1/highlighted_journal/

Global: Zendy Plus annual

Presents the access of premium content as premium feature

Premium Content

Presents the keyphrase highlighting as premium feature

Keyphrase Highlighting

Presents the summarisation as premium feature

Summarisation

Insights

Presents the pdf analysis as premium feature

PDF Analysis

Presents the zaia usage as premium feature

ZAIA

Global: Zendy Tools annual

Global: Zendy Free Plan

Global: Zendy Tools monthly

Global: Zendy Plus monthly

Fibroblast growth factor 23 (FGF23) is a potent regulator of phosphate (Pi) and vitamin D homeostasis. The transcription factor, early growth response 1 (egr-1), is a biomarker for FGF23-induced activation of the ERK1/2 signaling pathway. We have shown that ERK1/2 signaling blockade suppresses renal egr-1 gene expression and prevents FGF23-induced hypophosphatemia and 1,25-dihydroxyvitamin D (1,25(OH) 2 D) suppression in mice. To test whether egr-1 itself mediates these renal actions of FGF23, we administered FGF23 to  egr-1    -/-   and wild-type (WT) mice. In WT mice, FGF23 induced hypophosphatemia and suppressed expression of the renal Na/Pi cotransporters, Npt2a and Npt2c. In FGF23-treated  egr-1    -/-   mice, hypophosphatemic response was greatly blunted and Na/Pi cotransporter expression was not suppressed. In contrast, FGF23 induced equivalent suppression of serum 1,25(OH) 2 D concentrations by suppressing renal  cyp27b1  and stimulating c yp24a1  mRNA expression in both groups of mice. Thus, downstream of receptor binding and ERK1/2 signaling, we can distinguish the effector pathway that mediates FGF23-dependent inhibition of Pi transport from the pathway that mediates inhibition of 1,25(OH) 2 D synthesis in the kidney. Furthermore, we demonstrate that the hypophosphatemic effect of FGF23 is significantly blunted in  Hyp / egr-1    -/-   mice; specifically, serum Pi concentrations and renal Npt2a and Npt2c mRNA expression are significantly higher in  Hyp / egr-1    -/-   mice than in  Hyp  mice. We then characterized the egr-1 cistrome in the kidney using ChIP-sequencing and demonstrate recruitment of egr-1 to regulatory DNA elements in proximity to several genes involved in Pi transport. Thus, our data demonstrate that the effect of FGF23 on Pi homeostasis is mediated, at least in part, by activation of egr-1.

Characterization of FGF23-Dependent Egr-1 Cistrome in the Mouse Renal Proximal Tubule