Erythroid-produced intact FGF23 is a paracrine inhibitor of erythropoiesis.

Erythroid-produced intact FGF23 acts as a paracrine inhibitor of erythropoiesis, contributing to anemia in mice models of iron deficiency and chronic kidney disease.

• Why it matters: Understanding the distinct roles of bone- and erythroid-derived FGF23 is crucial because elevated circulating FGF23 is linked to impaired erythropoiesis in anemia conditions, yet their specific contributions remain unclear.
• What they did: The study used conditional gene deletions in mice to differentiate sources of FGF23, revealing that erythroid cells produce intact FGF23 that negatively impacts erythropoiesis through FGFR1 activation, especially under iron deficiency.
• The result: Erythroid-specific Fgf23 deletion alleviated anemia, while increased erythroid FGF23 worsened it, highlighting FGF23 as a potential target for treating anemia by modulating its paracrine effects on erythroid progenitors.