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Lipopolysaccharide potentiates the effect of hepatocyte growth factor on hepatocyte replication in rats by augmenting AP‐1 activity
Author(s) -
Gao Cuihua,
Jokerst Rodney,
Gondipalli Prathima,
Cai ShiRong,
Kennedy Susan,
Flye M. Wayne,
Ponder Katherine Parker
Publication year - 1999
Publication title -
hepatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.488
H-Index - 361
eISSN - 1527-3350
pISSN - 0270-9139
DOI - 10.1002/hep.510300602
Subject(s) - hepatocyte growth factor , hepatocyte , kinase , mapk/erk pathway , microbiology and biotechnology , stat3 , chemistry , liver regeneration , phosphorylation , signal transduction , dna synthesis , protein kinase a , biology , medicine , dna , biochemistry , receptor , regeneration (biology) , in vitro
The liver regenerates by replication of differentiated hepatocytes after damage or removal of part of the liver. Although several growth factors and signaling pathways are activated during regeneration, it is unclear as to which of these are essential for hepatocyte replication. We show here that low‐ (1 mg/kg) and high‐ (10 mg/kg) dose hepatocyte growth factor (HGF) induced replication of 2.1% and 11.1% of hepatocytes in rats, respectively. Lipopolysaccharide (LPS), an inducer of the acute phase response, augmented hepatocyte replication in response to low‐ and high‐dose HGF by 4‐ and 2‐fold, respectively. HGF alone induced moderate levels of c‐Jun‐N‐terminal kinase (JNK) and p44/p42 mitogen‐activated protein kinase (MAPK), resulting in moderate levels of AP‐1‐DNA binding activity. The combination of LPS + HGF increased JNK and AP‐1‐DNA binding activity more than levels seen with LPS or HGF alone. The activation of Stat3 that was observed after administration of LPS + HGF, but not HGF alone, could contribute to increased transcription of AP‐1 components. Because phosphorylation of the c‐Jun component of AP‐1 by JNK increases its ability to activate transcription, the AP‐1 in hepatocytes from animals treated with LPS + HGF may be more active than in rats treated with LPS or HGF alone. LPS may contribute to hepatocyte replication by potentiating the effect of HGF on the activation of both AP‐1‐DNA binding and transcriptional activity.