项目名称: Syndecan-4在椎间盘髓核细胞退变中生物学作用的机制研究
项目编号: No.81472132
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: 邹俊
作者单位: 苏州大学
项目金额: 72万元
中文摘要: 最新研究表明Syndecan-4可以加速椎间盘髓核细胞中蛋白聚糖的降解,导致细胞退变,但具体机制不详,相关的体内实验也未见报道。P53蛋白是一个非常重要的转录调节因子,参与细胞的多种重要的生理和病理过程。我们的预实验结果显示,过表达Syndecan-4能显著增加髓核细胞中的P53蛋白及其靶基因mdm2和P21的表达水平。为此,我们提出假说:Syndecan-4可能通过P53通路导致椎间盘髓核细胞退变。为了验证这一假说,我们将通过髓核细胞株和兔椎间盘退变模型,采用Real-time PCR、Western blot、病毒载体转染、RNA干扰、免疫共沉淀等手段,从分子、细胞、组织以及动物水平等层次探讨Syndecan-4在椎间盘髓核细胞退变中的作用,明确通过P53信号通路调控退变发生的机制。本研究将从Syndecan-4这个新视点为揭示椎间盘退变发生机制奠定基础,为椎间盘退变的诊治提供新的靶点。
中文关键词: 椎间盘退变;髓核细胞;信号通路;Syndecan-4
英文摘要: New researches show that Syndecan-4 can accelerate the degradation of aggrecan in the nucleus pulposus cells of intervertebral disc, leading to cell degeneration. However the precise mechanism is unknown, and in vivo study related has not been reported yet. P53 is very important transcription factor,which involved a variety of cellular biological processes. Our preliminary experimental results suggest that over-expression of Syndecan-4 significantly increased the expressions of P53 and its target genes mdm2 and P21.Therefore, we put forward the hypothesis: the Syndecan-4 leads to the intervertebral disc degeneration via P53 pathway. To test this hypothesis, we will explore the role of Syndecan-4 and the regulation mechanism of P53 signaling pathway in disc degeneration from the molecular, cell, tissue and animal levels, using Real-time PCR, Western blot, transfected, RNA interference, immunoprecipitation and others. This study will reveal the viewpoint from Syndecan-4 for disc degeneration, provide a new target for the treatment of intervertebral disc degeneration.
英文关键词: disc degeneration;nucleus pulposus cell;signaling pathway;Syndecan-4