关于肝纤维化和肝硬化的分子机制的当前数据未能完全解释其发展的所有阶段。已知单个基因和信号通路之间的相互作用在其功能中起重要作用。然而,关于他们关系的数据不足,而且往往相互矛盾。第一次,Notch1,Notch2,Yap1,Tweak(Tnfsf12)的mRNA表达,Fn14(Tnfrsf12a),Ang,Vegfa,Cxcl12(sdf),在Wistar大鼠中,在硫代乙酰胺诱导的肝纤维化的几个阶段详细研究了Nos2和Mmp-9。因子分析分离出三个因素,结合了高度相关的靶基因。第一个因素包括四个基因:Cxcl12(r=0.829,p<0.05),调整(r=0.841,p<0.05),Notch1(r=0.848,p<0.05),和Yap1(r=0.921,p<0.05)。第二个因素描述了Mmp-9(r=0.791,p<0.05)和Notch2(r=0.836,p<0.05)之间的相关性。第三个因素包括Ang(r=0.748,p<0.05)和Vegfa(r=0.679,p<0.05)。Nos2和Fn14基因不包括在任何因子中。通过mRNA表达水平的基因分组使得在由于肝毒性引起的纤维化变化的发展中,它们的产物之间可能存在致病关系。
Current data on the molecular mechanisms of liver fibrosis and cirrhosis fail to fully explain all stages of their development. Interactions between individual genes and signaling pathways are known to play an important role in their functions. However, data on their relationships are insufficient and often contradictory. For the first time, mRNA expression of Notch1, Notch2, Yap1, Tweak (Tnfsf12), Fn14 (Tnfrsf12a), Ang, Vegfa, Cxcl12 (Sdf), Nos2, and Mmp-9 was studied in detail at several stages of thioacetamide-induced liver fibrosis in Wistar rats. A factor analysis isolated three factors, which combined highly correlated target genes. The first factor included four genes: Cxcl12 (r = 0.829, p < 0.05), Tweak (r = 0.841, p < 0.05), Notch1 (r = 0.848, p < 0.05), and Yap1 (r = 0.921, p < 0.05). The second factor described the correlation between Mmp-9 (r = 0.791, p < 0.05) and Notch2 (r = 0.836, p < 0.05). The third factor included Ang (r = 0.748, p < 0.05) and Vegfa (r = 0.679, p < 0.05). The Nos2 and Fn14 genes were not included in any of the factors. The gene grouping by mRNA expression levels made it possible to assume a pathogenetic relationship between their products in the development of fibrotic changes due to liver toxicity.