Based on these data, we speculated that sGC/cGMP function on PKG activation to activate PPARγ, which attenuates hypoxia-induced HSCs activation and hepatic fibrogenesis. On the other side, hypoxia directly and indirectly inhibits the expression of PPAR, by inducing PI3K/AKT signaling or activating PDE5 to cGMP hydrolysis, which is ultimately beneficial to hypoxia-induced HSCs activation. Our findings may provide new insights into the mechanisms leading to fibrosis in the liver. It would be interesting to establish whether the same signals are operative in tissues in which both hypoxia and PPARγ are present, like in adipose tissue in obesity [31, 32]. New studies are necessary to address the potential of new therapeutic tools able to counteract the pathophysiological processes leading to fibrosis.