strategies to abrogate tgf- effects provide promising antifibrotic results , however , in vivo data regarding smad activation during fibrogenesis are scarce .
methods : here , liver fibrosis was assessed subsequent to bile duct ligation by determining liver enzymes in serum and collagen deposition in liver tissue .
activated hepatic stellate cells were identified by immunohistochemistry and immunoblots for alpha smooth muscle actin .
rtpcr for smad4 and smad7 was conducted with total rna and northern blot analysis for smad7 with mrna .
results : cholestasis induces tgf- signaling via smad3 in vivo , whereas smad2 phosphorylation was only marginally increased .
, negative feedback regulation of tgf- signaling by increased smad7 expression in activated hepatic stellate cells occurs , however does not interfere with fibrogenesis .
 abstractbackground / aims : profibrogenic tgf- signaling in hepatic stellate cells is modulated during transdifferentiation . 
 strategies to abrogate tgf- effects provide promising antifibrotic results , however , in vivo data regarding smad activation during fibrogenesis are scarce . 
 methods : here , liver fibrosis was assessed subsequent to bile duct ligation by determining liver enzymes in serum and collagen deposition in liver tissue . 
 activated hepatic stellate cells were identified by immunohistochemistry and immunoblots for alpha smooth muscle actin . 
 cellular localization of smad3 and smad7 proteins was demonstrated by immunohistochemistry . 
 rtpcr for smad4 and smad7 was conducted with total rna and northern blot analysis for smad7 with mrna . 
 whole liver lysates were prepared to detect smad2/3/4 and phospho- smad2/3 by western blotting . 
 results : cholestasis induces tgf- signaling via smad3 in vivo , whereas smad2 phosphorylation was only marginally increased . 
 smad4 expression levels were unchanged . 
 smad7 expression was continuously increasing with duration of cholestasis . 
 hepatocytes of fibrotic lesions exhibited nuclear staining smad3 . 
 in contrast to this , smad7 expression was localized to activated hepatic stellate cells . 
 conclusions : hepatocytes of damaged liver tissue display increased tgf- signaling via smad3 . further , negative feedback regulation of tgf- signaling by increased smad7 expression in activated hepatic stellate cells occurs , however does not interfere with fibrogenesis . 
Abstract
Background/Aims: