Fig. 5.

Model showing elevated calcium and/or phosphate up-regulate HGF secretion and c-Met activation in conjunction with activation of the PI3K/Akt signalling pathway, leading to SMC mineralisation, which can be inhibited by AdNK4 treatment. Signalling molecules and osteogenic transcription factors downstream of PI3K/Akt were shown to be involved in HGF/c-Met-induced mineralisation. We also show HGF/c-Met-induced Notch3 activation and using the Notch inhibitor, DAPT, we demonstrate attenuation of calcification suggesting Notch3 signalling involvement in this process. The dotted arrows between c-Met activation and HGF secretion indicate other factors could be associated with c-Met receptor and HGF ligand interaction.