Effect of glia maturation factor beta on the activation of hepatic stellate cells and on liver fibrosis / 中华肝脏病杂志

ABSTRACT

<p><b>OBJECTIVE</b>To further study the mechanism of the inhibitory effect of interferon beta-1a (IFN beta-1a) on the activation of human hepatic stellate cell (HSC) LX-2, and to analyze the differences on the protein expression in LX-2 induced by I IFN beta-1a.</p><p><b>METHODS</b>Cultured LX-2 cells were treated with 2000 U/ml IFN beta-1a for 48 h. Two-dimensional gel electrophoresis (2-DE) was performed to compare protein patterns of the control (untreated) and IFN beta-1a treated LX-2 and for quantitative and qualitative analyses of protein expression. A rat liver fibrosis model was established and the rats were sacrificed and their various tissues were obtained for the same analyses. Western blotting and RT-PCR were used to validate the expression of the changed proteins after treatment of IFN beta-1a in LX-2 cells and of various tissues of the rats.</p><p><b>RESULTS</b>708 +/- 25 spots were detected in control LX-2 cells and 804 +/- 32 spots in IFN beta-1a-treated LX-2 cells. A match rate of 73%-82% was achieved. The results also showed that 31 protein spots displayed quantitative changes in expression after IFN beta-1a treatment. Of the 31 spots, 21 proteins were identified, of which, one was newly found, two were enhanced in abundance and 18 showed lower expressions. The newly found protein was glia maturation factor beta (GMF beta). The treatment of LX-2 with IFN beta-1a increased the production of GMF beta(GMF beta) protein in comparison with the untreated cells (t=1.81, P < 0.01). The expression of GMF beta protein (1.81 vs 0.10) and mRNA (0.85 vs 0.12) were more in the normal liver tissues than in the cirrhotic liver tissues (t=2.53, 2.13 respectively, P < 0.01). The expressions of GMF beta protein and mRNA were weak in rat heart and lung tissues, however, they were strong in rat liver, kidney, spleen and brain tissues (t=1.91, 1.94 respectively, P < 0.01).</p><p><b>CONCLUSION</b>There is a significant difference of protein expression levels between IFN beta-1a untreated and treated LX-2 cells. These proteins, especially GMF beta, may be involved in an inhibition process of IFN beta-1a on activation and apoptosis of LX-2 cells. This proteome study may be useful in further studies of the relationship of IFN beta-1a treatment and human liver diseases.</p>