NF-kappaB activation in non-parenchymal liver cells after partial hepatectomy in rats: possible involvement in expression of heparin-binding epidermal growth factor-like growth factor.
OBJECTIVE
Nuclear factor (NF) B activation plays a critical role in the initiation of liver growth after partial hepatectomy (PH). However, the issue of where specifically NF-B is activated is unclear. We previously reported that heparin-binding epidermal growth factor-like growth factor (HB-EGF) is a hepatotrophic factor. The aims of this study were to identify NF-B-activated cells and to clarify their involvement in HB-EGF expression after PH.


METHODS
Using rats, a two-thirds PH was performed, after which NF-B-activated cells and HB-EGF-positive cells were identified by Southwestern histochemistry or immunohistochemistry. NF-B binding activity and HB-EGF gene expression were analyzed in rat hepatocytes and non-parenchymal cells (NPC) in primary culture.


RESULTS
NF-B was activated in Kupffer cells and sinusoidal endothelial cells prior to activation in hepatocytes. HB-EGF immunoreactivity was detected after NF-B activation in the sinusoidal cells from those localized in the periportal zones of hepatic lobules. HB-EGF gene expression by tumor necrosis factor was accompanied by an increase in NF-B binding activity in NPC but not in hepatocytes in primary culture, which was abolished by pyrrolidine dithiocarbamate, an inhibitor of NF-B activation. CONCLUSIONS; NF-B was activated in NPC prior to activation in hepatocytes. NF-B activation may be involved in HB-EGF expression in NPC after PH.
Sakuda
Shigeru
S
Department of Internal Medicine and Molecular Science, Graduate School of Medicine, Osaka University, 2-2 Yamadaoka, Suita, 565-0871 Osaka, Japan.
Tamura
Shinji
S
Yamada
Akira
A
Miyagawa
Jun-Ichiro
J
Yamamoto
Koji
K
Kiso
Shinichi
S
Ito
Nobuyuki
N
Higashiyama
Shigeki
S
Taniguchi
Naoyuki
N
Kawata
Sumio
S
Matsuzawa
Yuji
Y
D000818:Animals; D002478:Cells, Cultured; D004815:Epidermal Growth Factor / Q000235:genetics / Q000378:metabolism*; D015870:Gene Expression; D066257:Heparin-binding EGF-like Growth Factor; D006498:Hepatectomy / Q000379:methods*; D036341:Intercellular Signaling Peptides and Proteins; D008099:Liver / Q000378:metabolism*; D008297:Male; D016328:NF-kappa B / Q000502:physiology*; D011184:Postoperative Period; D051381:Rats; D017207:Rats, Sprague-Dawley
C587885:Hbegf protein, rat; D066257:Heparin-binding EGF-like Growth Factor; D036341:Intercellular Signaling Peptides and Proteins; D016328:NF-kappa B; D004815:Epidermal Growth Factor