Wnt antagonism inhibits hepatic stellate cell activation and liver fibrosis.

Activation of hepatic stellate cells (HSC), a key event in liver fibrosis, is caused by diminished adipogenic transcription. This study investigated whether Wnt signaling contributes to "antiadipogenic" activation of HSC and liver fibrogenesis. Culture-activated HSC from normal rats and HSC from cholestatic rat livers were examined for expression of Wnt, Frizzled (Fz) receptors, and coreceptors by quantitative PCR.

Inhibition of lipopolysaccharide-stimulated TNF-alpha promoter activity by S-adenosylmethionine and 5'-methylthioadenosine.

S-adenosylmethionine (SAM) is the principal biological methyl donor and precursor for polyamines. SAM is known to be hepatoprotective in many liver disease models in which TNF-alpha is implicated. The present study investigated whether and how SAM inhibited LPS-stimulated TNF-alpha expression in Kupffer cells (hepatic macrophages).

Tumor necrosis factor-alpha inhibits peroxisome proliferator-activated receptor gamma activity at a posttranslational level in hepatic stellate cells.

Diminished activity of peroxisome proliferator-activated receptor gamma (PPARgamma) is implicated in activation of hepatic stellate cells (HSC), a critical event in the development of liver fibrosis. In the present study, we investigated PPARgamma regulation by TNF-alpha in an HSC line designated as BSC. In BSC, TNF-alpha decreased both basal and ligand (GW1929)-induced PPARgamma mRNA levels without changing its protein expression.