糖皮质激素与转化生长因子β1协同上调PAI-1的机制及可能的生物学意义

项目名称： 糖皮质激素与转化生长因子β1协同上调PAI-1的机制及可能的生物学意义

项目编号： No.31301164

项目类型： 青年科学基金项目

立项/批准年度： 2014

项目学科： 生物科学

项目作者： 王燕

作者单位： 中国人民解放军第二军医大学

项目金额： 20万元

中文摘要： 糖皮质激素(GC)和转化生长因子β（TGFβ）在各自的受体介导下，通过激活信号转导通路，调节基因的表达产生生物学效应。两条通路间存在复杂的相互作用，根据组织细胞类型的不同和调节基因的不同，表现为相互拮抗和协同效应。纤溶酶原激活物抑制剂（PAI-1）是纤溶酶原激活物（PAs）的生理抑制剂，能抑制纤维蛋白和细胞外基质降解，从而促进基质的沉积和细胞的粘附。PAI-1对卵巢的正常功能和排卵机制中在时间和空间上的协调一致也起重要作用。本课题拟在前期发现GC和TGFβ1能协同上调卵巢癌细胞中PAI-1表达的基础上，进一步探讨在正常卵巢细胞和组织中GC和TGFβ对PAI-1表达的影响及其可能的机制与病理生理学意义。通过本课题的研究，有助于我们进一步了解GC/GR和TGFβ1信号通路的相互作用，以及这种相互作用对卵巢生理功能和卵巢癌生物学行为的影响，有重要的理论价值和临床意义。

中文关键词： 糖皮质激素；转化生长因子β1；纤溶酶原激活物抑制剂-1；磷酸化；卵巢癌

英文摘要： Glucocorticoid (GC) usually exerts its effects through the glucocorticoid receptor (GR). GC bound to GR which acts as a transcription factor, the glucocorticoid-receptor-complex is translocated to the nucleus and binds after dimerization to GC response elements (GREs) to regulate target genes. TGF-β can rapidly activate the transcription of a set of specific genes mediated through two types of transmembrane serine/threonine kinase receptors (type I and type II), and the highly conserved Smad family of proteins has been identified as intracellular signal transducers to relay the TGF-β signal to the nucleus. TGF-β and glucocorticoid signaling pathways interact both positively and negatively in regulating a variety of physiological and pathological processes.Plasminogen activator inhibitor type-1 (PAI-1) is a target gene of TGF-β which can also be regulated by GC. As the primary inhibitor of urokinase-type and tissue-type plasminogen activator (PAs), PAI-1, is generally regarded as a profibrotic factor because it retards ECM degradation by inhibiting the degrading enzymes. PAI-1 also plays an important role in the process of rat ovulation and as one of the marker for quality of ovum. We found that GC and TGFβ1 synergistically increase PAI-1 expression in ovarian cancer cells. Based on this issue, we will further ex

英文关键词： Glucocorticoid；Transforming growth factor beta；Plasminogen activator inhibitor-1；Phosphorylation；Ovarian cancer