CAJ | 학술논문

目的：研究结缔组织生长因子（CTGF）对大鼠肝星状细胞（HSC）迁移及基质金属蛋白酶2（MMP-2）表达及活化的影响。方法分别应用RT-PCR和Western blotting法检测MMP-2表达，明胶酶谱法检测MMP-2的活性；运用Western blotting法检测ERK1/2和Akt的磷酸化水平。运用Transwell小室检测肝星状细胞迁移能力。结果 CTGF呈剂量依赖性促进大鼠HSC中MMP-2 mRNA和蛋白表达；同时CTGF能够促进HSC迁移，MMP-2特异性抑制剂能够抑制CTGF的促迁移作用。ERK1/2和PI3K抑制剂能够显著抑制CTGF诱导的MMP-2表达以及CTGF促进HSC的迁移作用。结论 MMP-2表达和活性的增强在CTGF促进HSC迁移过程中发挥着重要作用，ERK1/2和PI3K信号通路在CTGF促进MMP-2表达发挥关键作用。
목적：연구결체조직생장인자（CTGF）대대서간성상세포（HSC）천이급기질금속단백매2（MMP-2）표체급활화적영향。방법분별응용RT-PCR화Western blotting법검측MMP-2표체，명효매보법검측MMP-2적활성；운용Western blotting법검측ERK1/2화Akt적린산화수평。운용Transwell소실검측간성상세포천이능력。결과 CTGF정제량의뢰성촉진대서HSC중MMP-2 mRNA화단백표체；동시CTGF능구촉진HSC천이，MMP-2특이성억제제능구억제CTGF적촉천이작용。ERK1/2화PI3K억제제능구현저억제CTGF유도적MMP-2표체이급CTGF촉진HSC적천이작용。결론 MMP-2표체화활성적증강재CTGF촉진HSC천이과정중발휘착중요작용，ERK1/2화PI3K신호통로재CTGF촉진MMP-2표체발휘관건작용。
Objective To identify the role of connective tissue growth factor (CTGF) in hepatic stellate cell (HSC) migration and its effects on gelatinase matrix metalloproteinase-2 (MMP-2) expression and activation. Methods The expression of MMP-2 was assessed by RT-PCR and Western blotting analyses. MMP-2 activity was evaluated by zymography. ERK1/2 and Akt phosphorylation were determined by Western blotting analysis. HSC migration was performed using Transwell cell culture chambers. Results The expression of MMP-2 mRNA and protein in HSCs were substantially increased by CTGF treatment in a dose-dependent manner. In addition, CTGF could promote HSC migration, and the addition of MMP-2-specific inhibitor impaired this phenomenon. To study the intracellular signaling pathways involved in CTGF-induced MMP-2 expression, we evaluated the effects of different kinase inhibitors. The inhibitors of extracellular signal-regulated kinase 1/2 (ERK1/2) and phosphatidyl inositol 3-kinase (PI3K) abrogated CTGF-elicited MMP-2 upregulation and significantly reduced CTGF-induced invasiveness of HSC. Conclusion MMP-2 plays an important role in the invasive effects of CTGF on HSC. ERK1/2 and PI3K are the main signals involved in CTFG-mediated MMP-2 expression.