结缔组织生长因子（CTGF)在再生障碍性贫血发病机制中的作用研究

项目名称： 结缔组织生长因子（CTGF)在再生障碍性贫血发病机制中的作用研究

项目编号： No.81500098

项目类型： 青年科学基金项目

立项/批准年度： 2016

项目学科： 医药、卫生

项目作者： 陈芳

作者单位： 中国医学科学院

项目金额： 18万元

中文摘要： 随着对再生障碍性贫血（AA）发病机制研究的不断深入，发现该病不仅存在造血干/祖细胞损伤，还涉及骨髓造血微环境的异常。再生障碍性贫血患者骨髓间充质干细胞(BM-MSC)在生物学特性和功能上几乎存在全方位异常。BM-MSC可以分泌产生丰富的结缔组织生长因子CTGF至骨髓微环境中。近年研究发现，小鼠BM-MSC转染shRNA沉默CTGF的表达后，细胞增殖受抑，向脂肪细胞分化显著增强。一系列的研究发现，CTGF不仅影响细胞的增殖，抑制细胞的脂肪分化，而且还可以抑制多种细胞凋亡，在体内和体外均促进血管新生。我们比较AA患者和正常人BM-MSC表达谱芯片，发现AA的BM-MSC中CTGF的mRNA表达水平比正常人显著减少。本项目，我们拟分析AA骨髓微环境中的CTGF水平和BM-MSC分泌表达CTGF的量和AA临床疾病参数的相关性，并且研究其与BM-MSC功能缺陷的关系，进一步探索AA病理机制。

中文关键词： 再生障碍性贫血；间充质干细胞；造血微环境；结缔组织生长因子

英文摘要： It's known that, in aplastic anemia, hematopoietic stem/progenitor cells are ordinarily injured by a viriety of adverse factors. Yet with the increasing research of pathological mechanisms of apalstic anemia (AA), abnormality of bone marrow hematopoietic microenvironment was also found to be involved in the development of this disease. Studies indicate that bone marrow-dirived mesenchymal stem cells (BM-MSC) manifest all kinds of defects including biological characteristics as well as cellular functions. BM-MSC are identified to secret abundant connective tissue growth factor (CTGF) into the hematopoietic microenvironment. In recent years, it was reported that in the BM-MSC of mouse origin, when expression of CTGF was silenced by infection of shRNA ,the cellular proliferation was dramatically inhibited and the cells underwent adipogenic differentiation easily. A series of research revealed that CTGF not only influenced cellular proliferation and adipogenic differentiation, but also inhibited cellular apoptosis and promoted angiogenesis in vitro as well as in vivo. Our examination of the mRNA microarry showed that mRNA expression level of CTGF in BM-MSC from AA patiants was largely reduced compared with the normal control. According to the literature and mRNA microarray results, in the current applicaion, we aim to measure the the concentration of CTGF in bone marrow microenvironment and the amount of CTGF that BM-MSC produce in vitro, then further explore its relationship with the functional defects of BM-MSC in AA and its possible participation in the pathogenesis of AA.

英文关键词： aplastic anemia;mesenchymal stem cells;hematopoietic microenvironment;connective tissue growth factor