To further confirm the above findings, we used zaprinast, a specific inhibitor of phosphodiesterase type 5 (PDE5), to inhibit cGMP hydrolysis and to observe the subsequent effects on PPARγ and PI3K/AKT signaling on hypoxia-induced HSC activation. Results showed that the hypoxic environment significantly improved the cGMP and PKG activity in HSCs (Figures 4(c)-4(d)). PDE5 inhibition restored cGMP and PKG activity (Figures 4(c)-4(d)), followed by increased PPARγ expression and repressed HSCs activation (decreased expression of α-SMA and desmin) (Figure 4(b)). These data suggested that sGC/cGMP/PKG and PI3K/AKT signals synergistically act on PPARγ, and the latter inhibited hypoxia-induced HSC activation.