Mechanisms of ductular reaction in non-alcoholic steatohepatitis

Figure 1 The different compartments of the ductular reaction, including hepatocyte self-proliferation and transdifferentiation, hepatic progenitor cell differentiation, and cholangiocyte proliferation and transdifferention. HPC: Hepatic progenitor cell.

Figure 2 A series of highly conserved signaling pathways in the ductular reaction which promotes the occurrence of non-alcoholic fatty liver disease and aggravates the prognosis of non-alcoholic steatohepatitis (Created with BioRender. com). A: The Notch signaling pathway regulates expression of genes, such as the Hes and Hey-related family, to determine cell differentiation and function, maintain liver homeostasis, repair liver damage, and regulate liver metabolism, inflammation, and cancer; B: The Hippo/YAP-TAZ signaling pathway can regulate liver size, metabolism, cell proliferation, cell migration, the epithelial-mesenchymal transition, and formation of the extracellular matrix and cytoskeleton formation, etc; C: The Wnt/β-catenin signaling pathway affects liver development and physiological functions of all liver disease stages, from initial injury and inflammation to fibrosis, cirrhosis and tumor occurrence; D: The hedgehog signaling pathway affects cell proliferation, migration, and differentiation; E: The HGF/c-Met signaling pathway activates multiple intracellular signaling pathways and affect cell proliferation, migration, and differentiation; F: The TWEAK/Fn14 signaling pathway regulates tissue inflammation and damage repair in addition to cell survival and death. HPC: Hepatic progenitor cell; NASH: Non-alcoholic steatohepatitis.