Figure 5.

Model of the cardioprotective action against anthracycline damage mediated by Met-Erk1,2-Timp1-Stat3 signaling in cardiac cells. HGF treatment stimulates the Met receptor that quickly leads to phosphorylation and nuclear translocation of Erk1,2. In the nucleus, Erk1,2 induces gene transcription of Timp1, the inhibitor of metalloproteases, which allows an endurable Met-dependent activation of Stat3. Thus, Met belatedly stimulates Stat3 and exerts cardioprotective functions. Black arrow lines indicate phosphorylation/activation. Dotted arrow line indicates activation within the cascade.