Links Between Hepatic Fibrosis, Ductular Reaction, and Progenitor Cell Expansion  Michael J. Williams, Andrew D. Clouston, Stuart J. Forbes  Gastroenterology  Volume 146, Issue 2, Pages 349-356 (February 2014) DOI: 10.1053/j.gastro.2013.11.034 Copyright © 2014 AGA Institute Terms and Conditions

Figure 1 Matrix changes and signaling in the HPC niche. The components of the HPC niche during both biliary and hepatocytic regeneration are shown. Hepatic stellate cells (HSCs) and collagen are associated with HPCs in biliary regeneration and macrophages (Mφ) with hepatocytic regeneration. A laminin-containing basement membrane is closely associated with HPCs in both processes. Although these 2 processes are shown separately for clarity, they may occur simultaneously during liver injury. In addition to altering the matrix, hepatic stellate cells and macrophages can send signals directly to, and receive signals from, HPCs. Candidate pathways that may either drive changes in matrix deposition and degradation or occur in parallel with these changes are shown. CTGF, connective tissue growth factor; EGF, epidermal growth factor; HGF, hepatocyte growth factor; HH, hedgehog; IGF, insulin-like growth factor; MCP-1, monocyte chemotactic protein 1; PDGF, platelet-derived growth factor; TIMP, tissue inhibitor of metalloproteinase; VEGF, vascular endothelial growth factor. Gastroenterology 2014 146, 349-356DOI: (10.1053/j.gastro.2013.11.034) Copyright © 2014 AGA Institute Terms and Conditions

Figure 2 Differences in matrix associated with the polarity of the ductular reaction. Keratin-7 staining (HPCs, brown) and hematoxylin–Van Gieson (collagen, pink) in a patient with alcoholic liver disease with septal fibrosis. Collagen deposition is densest around the biliary end of the ductular reaction, with little if any at the hepatocytic end (shown by arrow). Original magnification 400×. Gastroenterology 2014 146, 349-356DOI: (10.1053/j.gastro.2013.11.034) Copyright © 2014 AGA Institute Terms and Conditions