TY - JOUR
T1 - TWEAK and LTß signaling during chronic liver disease
AU - Dwyer, B.J.
AU - Olynyk, John
AU - Ramm, G.A.
AU - Tirnitz-Parker, Nina
PY - 2014
Y1 - 2014
N2 - Chronic liver diseases (CLD) such as hepatitis B and C virus infection, alcoholic liver disease, and non-alcoholic steatohepatitis are associated with hepatocellular necrosis, continual inflammation, and hepatic fibrosis. The induced microenvironment triggers the activation of liver-resident progenitor cells (LPCs) while hepatocyte replication is inhibited. In the early injury stages, LPCs regenerate the liver by proliferation, migration to sites of injury, and differentiation into functional biliary epithelial cells or hepatocytes. However, when this process becomes dysregulated, wound healing can progress to pathological fibrosis, cirrhosis, and eventually hepatocellular carcinoma. The other key mediators in the pathogenesis of progressive CLD are fibrosis-driving, activated hepatic stellate cells (HSCs) that usually proliferate in very close spatial association with LPCs. Recent studies from our group and others have suggested the potential for cytokine and chemokine cross-talk between LPCs and HSCs, which is mainly driven by the tumor necrosis factor (TNF) family members, TNF-like weak inducer of apoptosis (TWEAK) and lymphotoxin-ß, potentially dictating the pathological outcomes of chronic liver injury. © 2014 Dwyer, Olynyk, Ramm and Tirnitz-Parker.
AB - Chronic liver diseases (CLD) such as hepatitis B and C virus infection, alcoholic liver disease, and non-alcoholic steatohepatitis are associated with hepatocellular necrosis, continual inflammation, and hepatic fibrosis. The induced microenvironment triggers the activation of liver-resident progenitor cells (LPCs) while hepatocyte replication is inhibited. In the early injury stages, LPCs regenerate the liver by proliferation, migration to sites of injury, and differentiation into functional biliary epithelial cells or hepatocytes. However, when this process becomes dysregulated, wound healing can progress to pathological fibrosis, cirrhosis, and eventually hepatocellular carcinoma. The other key mediators in the pathogenesis of progressive CLD are fibrosis-driving, activated hepatic stellate cells (HSCs) that usually proliferate in very close spatial association with LPCs. Recent studies from our group and others have suggested the potential for cytokine and chemokine cross-talk between LPCs and HSCs, which is mainly driven by the tumor necrosis factor (TNF) family members, TNF-like weak inducer of apoptosis (TWEAK) and lymphotoxin-ß, potentially dictating the pathological outcomes of chronic liver injury. © 2014 Dwyer, Olynyk, Ramm and Tirnitz-Parker.
U2 - 10.3389/fimmu.2014.00039
DO - 10.3389/fimmu.2014.00039
M3 - Review article
C2 - 24592262
SN - 1664-3224
VL - 5
SP - 1
EP - 7
JO - Frontiers in Immunology
JF - Frontiers in Immunology
IS - FEB
ER -