Moreover, during ineffective erythropoiesis and observations on thalassemia patients the growth differentiation factor 15 (GDF15) and twisted gastrulation 1 (TWSG1
) are two transforming growth factor-beta (TGF) family products produced and they likewise down-regulate hepcidin.
Differently, beside sugar metabolism, several DF factors appeared to have a role in ossification and/or bone metabolism (HNRNPC, MRC2, RBMX, RRBP1, TNC, and TWSG1, Figure 3).
Of note, several proteins, which are involved in bone metabolism and ossification (HNRNPC, MRC2, RBMX, RRBP1, TNC, and TWSG1), were also highlighted.
In contrast, genes upregulated following LBH589 treatment included markers of osteoblast differentiation (RUNX2, ALPL, BMP4, and SPP1), positive regulators of skeletal and bone development or ossification (TWSG1
, SMAD3, TP63, and BMP2), and genes expressed by mature osteoblasts (IL6, LRP5, and CDH11) (Figure 2(c)).
Recent observations suggest that the erythropoietic signal may include 1 or more proteins released at sites of active erythropoiesis, i.e., growth differentiation factor-15 (growth differentiation factor-15 (GDF15) and twisted gastrulation protein homolog-1 (TWSG1).
GDF15 and TWSG1 are both BMP antagonists produced by erythroblasts and putative components of the erythroid regulator that can inhibit hepcidin expression in vitro.