Abstract
Background:
Hepatic fibrosis results from an imbalance between fibrogenesis and fibrolysis in the liver. The process of Ito cell activation, which is thought to be the central pathogenic mechanism in liver fibrogenesis/cirrhosis, may involve distinct interactions with Kupffer cells (KCs) mediated by various cytokines and growth factors. The aim of this study was to determine whether targeting KC function using GdCl3, which specifically acts on Kupffer cells, interferes with the manifastation of carbon tetrachloride (CCl4) and dimethylnitrosamine (DMN) induced hepatic fibrosis/cirrhosis.
Methods:
We assesed the change in distribution of ECM proteins, laminin and fibronectin and the marker of HSC activation, alpha-smooth muscle actin (α-SMA) after liver injury and after KC inactivator, GdCl3-treatment with light microscope immunohistochemistry. Using light microscopy, characteristic changes of fibrosis/cirrhosis were seen in the hepatotoxin-administrated groups.
Results:
The immunohistochemical profile of anti-laminin was significantly altered in hepototoxin-treated groups (p Conclusions:
The results suggest that GdCl3 suppressed the activation of lipocytes and their transition from hepatic lipocytes to myofibroblast-like cells in cirrhotic livers in CCl4-treated mice. These results support that treatment with the selective Kupffer cell toxicant GdCl3 prevents stellate cell activation and prevents liver fibrosis/cirrhosis