Smad mediates BMP-2-induced upregulation of FGF-evoked PC12 cell differentiation

We previously reported that bone morphogenetic protein (BMP)-2 augments fibroblast growth factor (FGF)-induced neuronal differentiation of PC12 cells by selectively upregulating FGF receptor (FGFR)-1 expression. Here we describe the underlying mechanism. BMP-2 activated Smad proteins in PC12 cells. Overexpression of Smad7 or Smad1, inhibitory and receptor-regulated isoforms, respectively, suppressed or enhanced BMP-2-induced upregulation of FGFR-1 expression. Smad 7 also inhibited the FGF-induced PC12 differentiation. Our findings indicate that activation of a Smad signaling pathway is required for upregulation of FGFR-1 expression by BMP-2 and for the synergistic induction of PC12 differentiation by BMP-2 and FGF.