血管外膜肌成纤维细胞分化相关蛋白研究

为寻找涉及血管紧张素II (AngII)和转化生长因子β1 (TGF-β1)诱导的血管肌成纤维细胞(MF)分化的蛋白, 本研究采用双向电泳和质谱从整体水平检测了MF分化前后蛋白表达谱的变化, 共找到41个差异表达的蛋白点, 表达水平和/或蛋白位置在Ang II和TGF-β1刺激后都发生明显变化的蛋白点14个, 4个蛋白上调, 6个蛋白下调, 2个蛋白位置发生明显变化, 2个蛋白表达上调，位置也发生变化; 只在Ang II诱导的MF中表达发生变化的蛋白20个, 只在TGF-β1诱导的MF中表达发生变化的蛋白7个. 选取Ang II和TGF-β1共同调节的14个蛋白进行质谱鉴定, 结果除骨架蛋白外, 首次发现MF分化同泛素蛋白酶体系统和嘌呤合成有关; septin 2的下调可能是成纤维细胞分化的标志. 本研究运用蛋白质组学技术发现了新的参与MF分化的蛋白质, 为进一步研究和干预细胞表型转化提供了新的思路和靶点.

Research on Proteins Associated to Differentiation of Vascular Ad-ventitial Myofibroblasts

In an attempt to identify proteins that could potentially be involved in differentiation of vascular adventitial myofibroblasts (MF), proteomic differential expression profile after stimulation to vascular adventitial fibroblasts (AF) with angiotensin II (Ang II) and transforming growth factor-beta 1 (TGF-β1) was investigated using two-dimensional electrophoresis (2D-E) and mass spectrometry. 41 protein spots with sig-nificant difference were identified. 14 of them were regulated obviously in abundance and/or position by both Ang II and TGF-β1. Among 14 spots, 4 protein spots were increased in abundance and that of other 6 spots were down-regulated. 2 spots with altered position and 2 proteins with both up-regulated abundance and altered position were also demonstrated. Moreover, the results exhibited 20 spots changed by Ang II and 7 spots changed by TGF-β1. 14 spots regulated by both Ang II and TGF-β1 were identified by mass spectrometry. Except for cytoskeleton proteins, it was first found that ubiquitin proteasome system and purine biosynthesis were required by differentiation of MF. Furthermore, decrease of septin 2 may be a marker in process of fibroblasts phenotypic transformation. Application of proteomic technique has displayed more novel proteins involved in MF differentiation, which provide new ideas and targets for investigating and intervening cell transformation.