胞外基质蛋白periostin在MSCs调控肠炎及其恶变过程中的功能研究

项目名称： 胞外基质蛋白periostin在MSCs调控肠炎及其恶变过程中的功能研究

项目编号： No.81470793

项目类型： 面上项目

立项/批准年度： 2015

项目学科： 医药、卫生

项目作者： 宋刚

作者单位： 厦门大学

项目金额： 73万元

中文摘要： Periostin是与肿瘤发生发展关系密切的细胞外基质分子，但其在肠炎发生及其恶变中的功能不清。前期研究发现MSCs在促进肠炎恶性转变过程中periostin表达呈现递增趋势。本项目充分利用periostin基因敲除小鼠和DSS、AOM/DSS诱导炎症及其相关性肠癌模型、periostin-/-肠上皮细胞、结肠癌细胞为研究对象，1）采取MSCs尾静脉注射、体外共培养等，明确periostin在MSCs调控肠炎发生和促进肠炎恶变过程中所介导的生物学功能；2）采用Co-IP、cDNA芯片和质谱检测等技术，筛选并鉴定periostin在调控炎症发生发展过程中起作用的受体，明确periostin及其受体共同参与的主要信号通路；3）结合临床肠炎及其肠癌相关标本进行上述分子机制的验证和临床意义分析，寻找包括periostin在内可能的分子作为慢性肠炎恶变的标志物，为其在临床医学上的应用奠定理论基础。

中文关键词： periostin；肠炎；间充质干细胞；炎症性肠癌

英文摘要： Recent clinical evidence and studies have revealed that the secreted protein periostin is involved in the development of various tumors including colon cancer. However, the functional mechanisms of periostin responsible for the colitis and its transformation and malignant progression are not clear. In our previous study, we found the tissue and serum periostin are higher in the colitis and its malignant transformation induced by MSCs compared to healthy control. It indicates that periostin plays very important roles in the progression of malignant transformation of colitis under the regulation of MSCs. So this proposal is focused on studying the colitis and colitis-associated cancer by using periostin conditional knockout mice models induced by DSS, AOM/DSS, periostin-/- colon epithelium cells and colon cancer cell line CT26. Firstly, we will confirm the biology functions of periostin responsible for MSCs mediated colitis and its transformation and malignant progression by using tail vein injection and cell co-cultured. And next, we will try to identify the periostin receptor involved in MSCs mediated colitis and its transformation and malignant progression by using Liquid chromatography-mass spectrometry (LC-MS) and co-immunoprecipitation (Co-IP). Furthermore, periostin and its receptors are involved in the main signal path will be confirmed and the function of MSCs in these pathways will be summarized. Simultaneously, we will further analyze some clinical samples of inflammatory bowel disease and colon cancer in order to verify molecular mechanisms and clinical significance. We expect to look for some potential proteins including periostin as a marker of colitis-associated cancer, in order to lay a foundation for the application of clinical medicine.

英文关键词： periostin;colitis;Mesenchymal Stem Cells(MSCs);colitis-associated cancer