Granulocyte-Macrophage Colony-Stimulating Factor Protects Dimethylnitrosamine-Induced Rat Liver Fibrosis By Inhibiting Transforming Growth Factor-β1 Signaling Pathway

Abstract Granulocyte-macrophage colony-stimulating factor (GM-CSF) exerts several therapeutic pharmacological effects but its role in liver fibrosis has not yet been studied. The current study investigates the inhibitory effects of GM-CSF on dimethylnitrosamine (DMN)-induced liver fibrosis in rats. In this study, liver fibrosis was induced in Sprague-Dawley rats by intraperitoneal injections of DMN (10 mg/kg of body weight) for three consecutive days per week for four weeks. To see the inhibitory effects on disease onset, GM-CSF (50 µg/kg of body weight) was injected for 2 consecutive days per week for 4 weeks along with DMN, while to see the therapeutic effects on disease progression, the GM-CSF injection was set forth at 4 weeks after the DMN injection. We found that DMN administration produced characteristics of molecular and pathological manifestations of liver fibrosis in rats including increased expressions of collagen I, alpha-smooth muscle actin (α-SMA), and transforming growth factor beta 1 (TGF-β1), and decreased PPAR-γ expression. Similarly, elevated serum levels of aspartate aminotransferase (AST), total bilirubin level (TBIL), and decreased albumin level (ALB) were observed. Treatment with GM-CSF improved the pathological liver conditions and significantly inhibited the elevated AST and TBIL, and increased ALB serum levels to normal. GM-CSF significantly decreased collagen I, α-SMA, and TGF-β1 expression and increased peroxisome proliferator-activated receptor gamma (PPAR-γ) expression. In conclusion, GM-CSF reduced the DMN-induced rat liver fibrosis by inhibiting TGF-β1 signaling pathway.