Figure 3. A schema showing the effects of ROS and other mediators on HSCs during liver injury.

Upon liver injury (e.g., CCl₄ administration), Kupffer cells, platelets and infiltrating blood cells such as monocytes and neutrophils produce several mediators including ROS and lipid peroxides. CCl₄ also causes hepatocyte apoptosis/necrosis, which release several mediators, including ROS and lipid peroxides. These mediators act on quiescent HSCs, which release retinoids and change their phenotype to myofibroblast-like cells. While these mediators continue to induce HSC activation, and also proliferation of activated HSCs and promote their fibrogenic activity, a subpopulation can undergo apoptosis in response to ROS challenge. NFkB, c-Myb, PI3K and ERK1/2 have been shown to participate in activation/proliferation of HSCs. See text for details.