Iron, inflammation, and fibroblast growth factor 23: Integrating molecular crosstalk, cardiovascular biology, and therapeutic perspectives

Table 4 Tissue context and receptor specificity of fibroblast growth factor 23 signaling

Receptor	Tissue	Alpha-Klotho context	Evidence and interpretation
FGFR1c	Renal tubular epithelium	Membrane-bound α-Klotho in canonical signaling	Structural, cellular, and animal evidence supports phosphate and vitamin D regulation[1,29,30]
FGFR4	Cardiomyocytes	Membrane α-Klotho not required in the cited models; soluble α-Klotho can modulate responses	Rodent/cell studies support hypertrophy and metabolic effects, with negative replication in other models; human benefit unproven[19,24,82,83]
FGFR4	Hepatocytes	Membrane α-Klotho-independent in the cited models	Cell and rodent evidence for inflammatory mediator production[3]
FGFR1	Erythroid progenitors	Requirement not established by the cited study	Mouse lineage deletion and progenitor culture support local inhibition of erythropoiesis[25]
FGFR1	Atrial fibroblasts and vascular smooth muscle	Do not infer independence without direct testing	Cell and animal evidence for proliferation or phenotype switching; these endpoints differ from calcification[88,93]
FGFR1	Coronary endothelial cells	Membrane α-Klotho detected; inhibition altered the response	Human cells in culture, not a clinical intervention: Context-dependent nitric oxide and redox effects[91]
FGFR2	Neutrophils	No α-Klotho requirement demonstrated here	Mouse and ex vivo human evidence for impaired integrin activation and recruitment[59]

These are selected experimentally implicated pathways, not an exhaustive receptor map. Human cells studied in culture are classified as cellular evidence. Absence of a demonstrated requirement is not proof of co-receptor independence. FGFR: Fibroblast growth factor receptor.