Survivin 在瘢痕疙瘩中的作用及机制研究

项目名称： Survivin 在瘢痕疙瘩中的作用及机制研究

项目编号： No.81201471

项目类型： 青年科学基金项目

立项/批准年度： 2013

项目学科： 医学四处

项目作者： 曹永倩

作者单位： 山东大学

项目金额： 25万元

中文摘要： 瘢痕疙瘩形成的重要机制之一即为成纤维细胞的过度增殖和凋亡受阻，瘢痕疙瘩成纤维细胞（KFB）具有肿瘤细胞的某些特征，因此抑制其增殖、诱导其凋亡一直是研究热点。近年来发现survivin基因在肿瘤细胞凋亡中发挥重要作用，但其在瘢痕疙瘩中的作用尚不清楚。申请者最近实验表明：与正常皮肤相比，survivin在瘢痕疙瘩组织中高表达，抑制其功能可抑制KFB的增殖，并促进其凋亡。 本课题以此为基础，首先检测survivin的特异性表达，并应用 survivin过表达载体和survivin-shRNA载体观察对KFB细胞生物学行为的影响及相关信号传导通路；最后应用裸鼠瘢痕疙瘩模型，观察survivin抑制剂的体内作用效果及其与皮质激素的协同作用。本项目从细胞、分子、动物模型和药物协同等多层面探讨survivin基因在瘢痕疙瘩中的作用，将有助于为探索瘢痕疙瘩的发病机制和治疗理念提供新思路。

中文关键词： 瘢痕疙瘩；成纤维细胞；survivin；凋亡；慢病毒

英文摘要： Over proliferation and apoptosis obstruction is one of the important mechanisms of keloid formation. As keloid fibroblasts (KFB) cells have some characteristics of tumor cells, how to inhibit production and induce apoptosis is the focus of keloid research. In recent years, survivin gene is found to play an important role in tumor apoptosis, but its role in keloid is not clear. Our recent experiments showed that compared with normal skin, survivin expression in keloid is obviously high, expression suppression of survivin could inhibit cell growth and induce apoptosis. Based on this, the research take KFB cells as the research object, firstly detect expression of survivin in keloid; and use survivin over expression vectors or survivin-shRNA carriers to observe the effect of them on KFB cell biology behaviors and related signaling pathways; finally animal model is applied to observe the effect of survivin inhibitor in vivo and its synergies with corticosteroid. The project try to discuss the role of survivin in keloid from cells, molecular, animal models and drug synergies levels, which is help to provides a new approach to explore the pathogenesis and treatment options of keloid.

英文关键词： keloid；fibroblast；survivin；apoptosis；lentivirus