Relationship between focal adhesion kinase and hepatic stellate cell proliferation during rat hepatic fibrogenesis.
OBJECTIVE
To investigate the dynamic expression of focal adhesion kinase (FAK) protein and FAK mRNA in fibrotic rat liver tissue, and the relationship between FAK and hepatic stellate cell (HSC) proliferation.


METHODS
Rat hepatic fibrosis was induced by bile duct ligation (BDL). Histopathological changes were evaluated by hematoxylin and eosin staining, and by Masson's trichrome method. FAK mRNA in the rat livers was determined by reverse transcription-polymerase chain reaction (RT-PCR), and the distributions of FAK were assessed immunohistochemistrically. The number of activated HSCs was quantified after alpha smooth muscle actin (alpha-SMA) staining.


RESULTS
With the development of hepatic fibrosis, the positively stained cells of alpha-SMA increased obviously, which were mainly resided in the portal ducts, fiber septa and perisinuses accompanied with proliferating bile ducts. The positively stained areas of the rat livers in model groups 1 to 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). The positive staining for FAK significantly increased, which was mainly situated in portal ducts, fiber septa and around the bile ducts, vascular endothelial cells and perisinusoidal cells. The expression of FAK was positively correlated with alpha-SMA expression (r = 0.963, P<0.05). FAK mRNA expression was obviously up-regulated in the model groups compared to the control group.


CONCLUSIONS
These data suggest that expressions of FAK protein and mRNA are greatly increased in fibrotic rat livers, which may play an important role in HSC proliferation and hepatic fibrogenesis.
Jiang
Hui-Qing
HQ
Department of Gastroenterology, The Second Hospital of Hebei Medical University, Shijiazhuang 050000, Hebei Province, China. huiqingj@heinfo.net
Zhang
Xiao-Lan
XL
Liu
Li
L
Yang
Chang-Chun
CC
D000199:Actins / Q000378:metabolism*; D000818:Animals; D015415:Biomarkers; D049109:Cell Proliferation; D051417:Focal Adhesion Kinase 1; D051416:Focal Adhesion Protein-Tyrosine Kinases; D007150:Immunohistochemistry; D008099:Liver / Q000166:cytology / Q000201:enzymology / Q000473:pathology; D008106:Liver Cirrhosis, Experimental / Q000201:enzymology* / Q000473:pathology; D008297:Male; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction
D000199:Actins; D015415:Biomarkers; D011505:Protein-Tyrosine Kinases; D051417:Focal Adhesion Kinase 1; D051416:Focal Adhesion Protein-Tyrosine Kinases; C496052:Ptk2 protein, rat