Liver knockout YAP gene improved insulin resistance induced hepatic fibrosis.

Abstract

Yes-associated protein (YAP), as a co-activator of transcription factors, is a downstream protein in the Hippo signaling pathway with important functions in cell proliferation, apoptosis, invasion and migration. YAP also plays a key role in the development of CCl4 induced liver fibrosis. However, the mechanism of YAP during the hepatic fibrosis progression and reversion is still unclear. Mild liver fibrosis was developed after 4M (month) high fat diet (HFD) stimulation, and we found that YAP signaling pathway was activated. Here, we aimed to reveal whether liver specifically knockout of YAP gene in the liver can improve liver fibrosis induced by insulin resistance (IR) using HFD stimulation, and further to explain its specific mechanism. We found that liver specific YAP gene knock-out improved IR-induced liver fibrosis and liver dysfunction, which mechanism is related to the inhibition of insulin signal pathway at FoxO1 level. These findings provide a new idea, and YAP is expected to be a new target to reverse the early stage of liver fibrosis induced by IR.