TY - JOUR
T1 - Cirrhotic hepatocytes exhibit decreased TGFβ growth inhibition associated with downregulated Smad protein expression
AU - Lange, Patricia A.
AU - Samson, Charles M.
AU - Bird, Mark A.
AU - Hayden, Melissa A.
AU - Behrns, Kevin E.
PY - 2004/1/16
Y1 - 2004/1/16
N2 - TGFβ controls hepatocyte growth through cell cycle arrest and apoptosis, and resistance to TGFβ is a mechanism of malignant transformation. The aim of this study was to assess differences in TGFβ-mediated growth inhibition in normal and cirrhotic hepatocytes. Cirrhosis was induced in mice and normal and cirrhotic hepatocytes were isolated by collagenase perfusion and treated with or without TGFβ (5ng/ml). DNA synthesis, Smad protein expression, and DNA binding activity were determined. TGFβ reduced DNA synthesis to a greater degree in normal hepatocytes than in cirrhotic hepatocytes (87% vs. 68%; p<0.05). Smad protein expression was decreased in cirrhotic hepatocytes and Smad 2/3/4 complex formation was suppressed. Furthermore, cirrhotic hepatocytes had decreased DNA binding activity at 120min following TGFβ treatment. In conclusion, decreased Smad protein expression may impair TGFβ-mediated growth inhibition in cirrhotic hepatocytes.
AB - TGFβ controls hepatocyte growth through cell cycle arrest and apoptosis, and resistance to TGFβ is a mechanism of malignant transformation. The aim of this study was to assess differences in TGFβ-mediated growth inhibition in normal and cirrhotic hepatocytes. Cirrhosis was induced in mice and normal and cirrhotic hepatocytes were isolated by collagenase perfusion and treated with or without TGFβ (5ng/ml). DNA synthesis, Smad protein expression, and DNA binding activity were determined. TGFβ reduced DNA synthesis to a greater degree in normal hepatocytes than in cirrhotic hepatocytes (87% vs. 68%; p<0.05). Smad protein expression was decreased in cirrhotic hepatocytes and Smad 2/3/4 complex formation was suppressed. Furthermore, cirrhotic hepatocytes had decreased DNA binding activity at 120min following TGFβ treatment. In conclusion, decreased Smad protein expression may impair TGFβ-mediated growth inhibition in cirrhotic hepatocytes.
UR - http://www.scopus.com/inward/record.url?scp=0346433829&partnerID=8YFLogxK
U2 - 10.1016/j.bbrc.2003.12.003
DO - 10.1016/j.bbrc.2003.12.003
M3 - Article
C2 - 14697224
AN - SCOPUS:0346433829
SN - 0006-291X
VL - 313
SP - 546
EP - 551
JO - Biochemical and Biophysical Research Communications
JF - Biochemical and Biophysical Research Communications
IS - 3
ER -