Figure 7.

Schematic representing the ET_AR/G_αq/ERK signaling pathway for ET-1-inducd fibroblast activation and myofibroblast differentiation. ET-1 binding to ET_ARs leads to an activation of heterotrimeric G_q protein, resulting in the dissociation of the G_αq protein from the G_βγ subunit. The activated G_αq proteins transduced the signal through ERK1/2, which in turn induced fibroblast activation and myofibroblast differentiation. Interestingly, ETR antagonism using ERAs, ambrisentan and bosentan, exhibits cardioprotective effects by prevention and restoration of fibrotic actions of ET-1 in human cardiac fibroblasts. α-SMA: α-smooth muscle actin; ET-1: Endothelin-1; ERAs: endothelin receptor antagonists.