TY - JOUR
T1 - Tumor necrosis factor-α induces c-jun during the regenerative response to liver injury
AU - Diehl, A. M.
AU - Yin, M.
AU - Fleckenstein, J.
AU - Yang, S. Q.
AU - Lin, H. Z.
AU - Brenner, D. A.
AU - Westwick, J.
AU - Bagby, G.
AU - Nelson, S.
PY - 1994
Y1 - 1994
N2 - After liver injury, remaining hepatocytes proliferate to regenerate the liver. Although the precise mechanisms that initiate and localize regeneration are unknown, local induction of c-jun is a critical, early step in the response. Treatment of rats with antibodies to tumor necrosis factor- α (TNF-α), a mediator of liver injury, inhibits regenerative induction of jun nuclear kinase activity and nuclear c-jun expression and alters the DNA binding activity of the c-jun transcription factor, AP-1, in liver. Pretreatment with anti-TNF antibodies does not affect pulmonary or renal c- jun expression or AP-1 binding activity post-partial hepatectomy. In primary hepatocyte cultures, TNF-α directly promotes the proliferative actions of mitogens, supporting in vivo evidence that it sensitizes hepatocytes to mitogens. Thus local release of TNF may act in a paracrine fashion to initiate regeneration in the injured liver by promoting induction of critical growth-related genes, such as c-jun.
AB - After liver injury, remaining hepatocytes proliferate to regenerate the liver. Although the precise mechanisms that initiate and localize regeneration are unknown, local induction of c-jun is a critical, early step in the response. Treatment of rats with antibodies to tumor necrosis factor- α (TNF-α), a mediator of liver injury, inhibits regenerative induction of jun nuclear kinase activity and nuclear c-jun expression and alters the DNA binding activity of the c-jun transcription factor, AP-1, in liver. Pretreatment with anti-TNF antibodies does not affect pulmonary or renal c- jun expression or AP-1 binding activity post-partial hepatectomy. In primary hepatocyte cultures, TNF-α directly promotes the proliferative actions of mitogens, supporting in vivo evidence that it sensitizes hepatocytes to mitogens. Thus local release of TNF may act in a paracrine fashion to initiate regeneration in the injured liver by promoting induction of critical growth-related genes, such as c-jun.
KW - cytokines
KW - proliferation
UR - http://www.scopus.com/inward/record.url?scp=0028518860&partnerID=8YFLogxK
U2 - 10.1152/ajpgi.1994.267.4.g552
DO - 10.1152/ajpgi.1994.267.4.g552
M3 - Article
C2 - 7943321
AN - SCOPUS:0028518860
VL - 267
SP - G552-G561
JO - American Journal of Physiology - Gastrointestinal and Liver Physiology
JF - American Journal of Physiology - Gastrointestinal and Liver Physiology
SN - 0193-1857
IS - 4 30-4
ER -