Activation of signal transducer and activator transcription 3 and expression of suppressor of cytokine signal 1 during liver regeneration in rats.
OBJECTIVE
Recent work has shown that the signal transducer and activator of transcription (STAT) 3 activation is important for the initiation of the proliferative response following partial hepatectomy (PH). However, the issue of where STAT3 is activated and how it is regulated is unclear. The aims of this study were to identify STAT3-activated cells and to clarify the expression of suppressor of cytokine signal (SOCS), a negative feedback molecule of STAT3, after PH.


METHODS
STAT3-activated cells and SOCS1-positive cells were identified by immunohistochemistry after a two-thirds PH in rats. SOCS mRNA was examined by Northern analysis.


RESULTS
STAT3 was activated in hepatocytes from those localized in the periportal zones of hepatic lobules after PH. STAT3 activation was also detected in Kupffer cells and sinusoidal endothelial cells prior to its detection in hepatocytes. After STAT3 activation, SOCS1 protein in response to PH was detected immunohistochemically in regenerating liver. SOCS1 and SOCS3 mRNA were induced in regenerating liver after PH.


CONCLUSIONS
STAT3 signaling can occur in Kupffer cells and sinusoidal endothelial cells prior to in hepatocytes from those localized in the periportal zones. SOCS1 as well as SOCS3 may regulate STAT3 signaling negatively 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
Ji
Yamamoto
Koji
K
Kiso
Shinichi
S
Ito
Nobuyuki
N
Imanaka
Kazuho
K
Wada
Akira
A
Naka
Tetsuji
T
Kishimoto
Tadamitsu
T
Kawata
Sumio
S
Matsuzawa
Yuji
Y
D000818:Animals; D015152:Blotting, Northern; D002352:Carrier Proteins / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000378:metabolism*; D015870:Gene Expression / Q000502:physiology; D022781:Hepatocytes / Q000737:chemistry / Q000378:metabolism; D006863:Hydrogen-Ion Concentration; D007150:Immunohistochemistry; D007728:Kupffer Cells / Q000737:chemistry / Q000378:metabolism; D008115:Liver Regeneration / Q000502:physiology*; D008297:Male; D011506:Proteins / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D012097:Repressor Proteins; D050796:STAT3 Transcription Factor; D015398:Signal Transduction / Q000502:physiology*; D000071222:Suppressor of Cytokine Signaling 1 Protein; D000071223:Suppressor of Cytokine Signaling 3 Protein; D050826:Suppressor of Cytokine Signaling Proteins; D015534:Trans-Activators / Q000378:metabolism*; D014157:Transcription Factors
D002352:Carrier Proteins; D004268:DNA-Binding Proteins; D011506:Proteins; D012333:RNA, Messenger; D012097:Repressor Proteins; D050796:STAT3 Transcription Factor; C491589:Socs1 protein, rat; C491408:Socs2 protein, rat; C491410:Socs3 protein, rat; C494088:Stat3 protein, rat; D000071222:Suppressor of Cytokine Signaling 1 Protein; D000071223:Suppressor of Cytokine Signaling 3 Protein; D050826:Suppressor of Cytokine Signaling Proteins; D015534:Trans-Activators; D014157:Transcription Factors