Figure 7. A diagram illustrating different regenerative responses in hepatocyte Yap1 specific KO and wild type mice during liver injury.

Yap protein is activated upon hepatocyte damage caused by insults such as ethanol and carbon tetrachloride. Active Yap has been known to form complexes with TEAD transcriptional factors in nucleus and mediate transcriptional reprograming leading to hepatocyte proliferation and progenitor cell activation. Moreover, the active Yap can transcriptionally activate target genes, including Aldh1a1 that encodes an enzyme for removal of toxic aldehydes during hepatocyte damage. However, Yap1 hepatocyte specific KO loses normal regeneration ability. Without Yap, target genes such as Aldh1a1 can’t be induced for effective removal of toxic aldehydes. The impaired regeneration eventually causes susceptibility to hepatotoxicity, hemorrhages, hypoxia, activation of stromal cells and abnormal ECM remodeling.