GDP-L-fucose synthase (FX protein) is a novel dual modulator of calcium oxalate kidney stone-forming processes

GDP-L-fucose synthase (or FX protein) has recently been identified in the urine from subjects with calcium oxalate (CaOx) kidney stones, but not in the normal urine. However, its role in kidney stone formation was unknown. We, therefore, produced and purified recombinant human FX protein and examined its stone-modulating effects using various assays compared with blank and negative controls. Crystal assays revealed that the FX protein promoted CaOx crystallization, crystal aggregation and crystal invasion through extracellular matrix (ECM). On the other hand, FX inhibited CaOx crystal growth and crystal-cell adhesion. Potential mechanisms underlying its crystal modulation were investigated. Ca²⁺- and Ox^2--binding affinity assays demonstrated that FX effectively bound both Ca²⁺ and Ox^2- ions. Immunofluorescence staining using a monoclonal antibody specific to the human FX protein revealed the direct binding of this protein to CaOx crystal surfaces. In conclusion, our findings indicate that the human FX protein is a novel dual CaOx stone modulator. While it promotes crystallization, aggregation and ECM invasion of CaOx crystals, it inhibits the crystal growth and adhesion to renal cells via the binding with free Ca²⁺ and Ox^2- ions as well as the crystal surfaces.