Dynamic expression of extracellular signal-regulated kinase in rat liver tissue during hepatic fibrogenesis.

摘要

AIM: 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). CONCLUSION: 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.