MAPK8 and Hepatic fibrosis: In fibrotic livers, TGF-β1 expression increases markedly with fibrogenic activity.553–556 Induction of TGF-β1 expression in murine livers leads to hepatic fibrosis characterized by prominent ECM deposition in peri-sinusoidal areas with activation of HSCs and apoptosis of hepatocytes.557,558 Notably, activated HSCs which play a major role in hepatic fibrosis can provide an important source of TGF-β,559 while overproduced TGF-β can in turn activate several signaling pathways such as those of SMAD, MEK, JNK, PI3K, and JAK/STAT in HSCs to contribute to their functions.236,237