We dissected the cellular and molecular mechanisms underlying the therapeutic effect of FGF23, and demonstrated a klotho-independent, causal role for FGF23 in the suppression of SDF-1/CXCR4 via inhibition of a non-canonical Erk/RSK/NF-κB phosphorylation, and suggested that FGF23 contributes to the decrease of SDF-1-induced senescence of EPCs as a contributor for renoprotection during AKI (Supplementary Fig. 9). This evidence concerns the gene FGF23 and acute kidney injury.