Dynamic expression of extracellular signal-regulated kinase in rat liver tissue during hepatic fibrogenesis.
OBJECTIVE
To investigate whether extracellular signal-regulated kinase 1 (ERK(1)) is activated and associated with hepatic stellate cell (HSC) proliferation in fibrotic rat liver tissue.


METHODS
Rat hepatic fibrosis was induced by bile duct ligation (BDL). Histopathological changes were evaluated by hematoxylin and eosin staining, and Masson's trichrome method. ERK(1) mRNA in rat liver tissue was determined by reverse transcription-polymerase chain reaction, while the distribution of ERK(1) was assessed by immunohistochemistry. ERK(1) protein was detected by Western blotting analysis. The number of activated HSCs was quantified after alpha smooth muscle actin (alpha-SMA) staining.


RESULTS
With the development of hepatic fibrosis, the positive staining cells of alpha-SMA increased obviously, and mainly resided in the portal ducts. Fiber septa and perisinuses were accompanied with proliferating bile ducts. The positive staining areas of the rat livers in model groups 1-4 wk after ligation of common bile duct (12.88% +/- 2.63%, 22.65% +/- 2.16%, 27.45% +/- 1.86%, 35.25% +/- 2.34%, respectively) were significantly larger than those in the control group (5.88% +/- 1.46%, P < 0.01). With the development of hepatic fibrosis, the positive cells of ERK(1) increased a lot, and were mainly distributed in portal ducts, fiber septa around the bile ducts, vascular endothelial cells and perisinusoidal cells. Western blotting analysis displayed that the expression of ERK(1) and ERK(2) protein was up-regulated during the model course, and its level was the highest 4 wk after operation, being 3.9-fold and 7.2-fold higher in fibrotic rat liver than in controls. ERK(1) mRNA was expressed in normal rat livers as well, which was up-regulated two days after BDL and reached the highest 4 wk after BDL. The expression of ERK(1) was positively correlated with alpha-SMA expression (r = 0.958, P < 0.05).


CONCLUSIONS
The expression of ERK(1) protein and mRNA is greatly increased in fibrotic rat liver tissues, which may play a key role in HSC proliferation and hepatic fibrogenesis.
Zhang
Xiao-Lan
XL
Department of Gastroenterology, the Second Hospital of Hebei Medical University, Shijiazhuang 050000, Hebei Province, China. xiaolanzh@126.com
Liu
Jin-Ming
JM
Yang
Chang-Chun
CC
Zheng
Yi-Lin
YL
Liu
Li
L
Wang
Zhan-Kui
ZK
Jiang
Hui-Qing
HQ
D000199:Actins / Q000235:genetics / Q000378:metabolism; D000818:Animals; D049109:Cell Proliferation; D015971:Gene Expression Regulation, Enzymologic / Q000235:genetics; D022781:Hepatocytes / Q000378:metabolism / Q000473:pathology; D008099:Liver / Q000201:enzymology* / Q000378:metabolism / Q000473:pathology; D008103:Liver Cirrhosis / Q000201:enzymology* / Q000378:metabolism / Q000473:pathology; D008297:Male; D048052:Mitogen-Activated Protein Kinase 3 / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley
D000199:Actins; D012333:RNA, Messenger; D048052:Mitogen-Activated Protein Kinase 3