Expression of stem cell factor and its receptor, c-kit, in different rat models of liver injury and regeneration

Aims: Stem cell factor (SCF) and its receptor c-kit constitute an important signal transduction system implicated in survival, proliferation and differentiation. However, the changes of the gene expression of the SCF/c-kit gene-system in normal liver, under different conditions of liver injury and regeneration and in different liver cells have not yet been determined.

EXPERIMENTAL DESIGN: The expression of SCF and c-kit genes was examined in normal rat liver, in acute phase model of turpentine oil intramuscular injection, in acute and chronic CCl₄-induced liver injury, in rat models utilizing partial hepatectomy (PH) with or without administration of 2-acetylaminofluorene (AAF). Furthermore, the expression of the SCF/c-kit system was studied in isolated, cultured rat liver cells.

Results: In the normal rat liver significant c-kit mRNA expression was detected, while SCF gene expression was lower. Under acute phase conditions no significant changes were found in the expression of the SCF/c-kit system. In the injured rat liver and after conventional 70% partial hepatectomy up to 2-fold upregulation of c-kit was found, whereas in the chronic CCl₄-induced liver injury, SCF was significantly upregulated. Surprisingly, in rat models utilizing partial hepatectomy (PH) combined with the administration of 2-acetylaminofluorene (AAF), the maximum of c-kit induction, which happened at day 7 after PH, was 32-fold increased related to control rat liver, whereas SCF was 340-fold elevated at the same time point. Isolation of different liver cells demonstrated a significant coexpression of stem cell factor and its receptor c-kit in sinusoidal endothelial cells and Kupffer cells, whereas passaged and cultured liver myofibroblasts expressed only SCF. Interestingly, the acute phase cytokine: interleukin–1-beta significantly induced the expression of both c-kit and SCF genes in isolated rat hepatocytes.

Conclusion: The SCF/c-kit system, possibly with the contribution of endothelial-, Kupffer cells, hepatocytes and liver myofibroblasts may have a growth-regulating role during different conditions of liver regeneration, and especially when hepatocellular regeneration is suppressed.

c-kit - liver regeneration - stem cell factor