血管外膜肌成纤维细胞分化相关蛋白研究  

Research on Proteins Associated to Differentiation of Vascular Adventitial Myofibroblasts

作　　者：郭淑杰[1,2] 吴凌云 魏坚[1] 高平进[1,2] 朱鼎良[1] 

机构地区：[1]上海交通大学医学院附属瑞金医院上海市高血压研究所上海市血管生物学重点实验室国家医学基因组学重点实验室 [2]中国科学院上海生命科学研究院上海交通大学医学院健康科学研究所血管生物学实验室上海200025 [3]中国科学院上海生命科学研究院上海交通大学医学院健康科学研究所血管生物学实验室

出　　处：《化学学报》2007年第15期1504-1510,共7页Acta Chimica Sinica

基　　金：国家重点基础研究项目(Nos.2004CB518603;2006CB503804);国家高技术研究发展计划(No.2006AA02Z179);上海市科委基础研究重点项目(No.05JC14038);上海市教委青年基金(No.05BZ10)资助项目.

摘　　要：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AngII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AngII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AngII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;septin2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.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 significant 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.

关 键 词：外膜 成纤维细胞 分化 AngⅡ TGF-Β1 双向电泳 质谱 

分 类 号：R341[医药卫生—基础医学]