Figure 2.
The N-terminal domain of ERFE is sufficient to suppress hepcidin. (A) Structure of human ERFE, containing a signal peptide (SP), N-terminal region (NTD) with a collagen-like domain (6 GXY), and a globular C1q domain (gC1Q). The location of the 2 predicted furin cleavage sites are indicated (RARR and RLRR). ERFE subunits designed and expressed based on predicted furin cleavage sites (F1-F5). (B) Huh7 cells were treated for 24 hours with 1 µg/mL of ERFE subunits F1 to F5, full-length or vehicle, and analyzed for HAMP gene expression. (C) Wild-type mice were treated intraperitoneally with 100 µg of F2 ERFE or saline and analyzed 3 hours after treatment for liver gene expression of 5 BMP target genes (Hamp1, Id1, Id2, Atoh8, Smad7) and Bmp2 and Bmp6. Columns represent mean ± standard deviation. n = 3 replicates per group, panel B; n = 6 mice per group, panel C. *P < .05; **P < .01; ***P < .001; ****P < .0001 using the Student t test.

The N-terminal domain of ERFE is sufficient to suppress hepcidin. (A) Structure of human ERFE, containing a signal peptide (SP), N-terminal region (NTD) with a collagen-like domain (6 GXY), and a globular C1q domain (gC1Q). The location of the 2 predicted furin cleavage sites are indicated (RARR and RLRR). ERFE subunits designed and expressed based on predicted furin cleavage sites (F1-F5). (B) Huh7 cells were treated for 24 hours with 1 µg/mL of ERFE subunits F1 to F5, full-length or vehicle, and analyzed for HAMP gene expression. (C) Wild-type mice were treated intraperitoneally with 100 µg of F2 ERFE or saline and analyzed 3 hours after treatment for liver gene expression of 5 BMP target genes (Hamp1, Id1, Id2, Atoh8, Smad7) and Bmp2 and Bmp6. Columns represent mean ± standard deviation. n = 3 replicates per group, panel B; n = 6 mice per group, panel C. *P < .05; **P < .01; ***P < .001; ****P < .0001 using the Student t test.

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