Figure 6.
Cter-FGF23 peptides antagonize BMP2/9-induced hepcidin secretion. Time course of serum (A) BMP2 and (B) BMP9, mRNA expression of (C) Bmp2 and (D) Bmp9 in selected organs and time course mRNA expression of liver (E) Bmp2 and (F) Bmp9 in 6-week-old WT mice, 6 hours after administration of a single dose of 250 ng/g IL-1β. Liver (G) Hamp mRNA expression and serum (H) hepcidin, (I) iron and (J) TSAT and (K) phosphate in 6-week-old WT mice 6 hours after administration of a single dose of 50 ng/g Cter-FGF23, 10 ng/g BMP (2, 6 or 9), or both. n ≥ 5 per group. Expression of (L) Hamp mRNA in primary hepatocytes treated with Cter-FGF23 (50 ng/mL), 10 ng/mL BMP (2, 6 or 9) or both for 6 and 24 hours. n ≥ 5 per group. P < .05 vs (∗) Ctr T0, (a) Ctr NaCl, (b) Ctr Cter-FGF23, (c) BMP (2, 6, 9). (M) iFGF23 predicted 3D structure, (N) Cter-FGF23 isolated from panel M, (O) predicted AlphaFold2 Cter-FGF23 structure (model 0), (P) BMP2 dimer (blue) binding BMPR-II (purple) and BMPR-IA (red), (Q) Interaction of 2 molecules of Cter-FGF23 with a dimeric BMP2 at the BMPR-II site, (R) Interaction of 2 molecules of Cter-FGF23 with a dimeric BMP9.