MicroRNA184在角膜新生血管形成中的作用及机制研究

MicroRNAs (miRNAs) are small, noncoding, endogenic RNAs of 21–25 nucleotides in length. MicroRNAs play important roles in the cell proliferation and differentiation, development by regulating the targeted genes at posttranscriptional level. Earlier studies have demonstrated that miR-184 is preferentially expressed in the cornea, while the role of miR-184 in the formation of corneal neovascularization remains unknown. Recently, we investigated the role of miR-184 in the cornea neovascularization using a rat corneal suture model. Interestingly, our latest preliminary data showed that the miR-184 level was significantly decreased induced by suture and miR-184 targeted gene expression, such as Wnt signaling pathway factor was also upregulated. We thus hypothesized that miR184 plays a vital role in the corneal neovascularization probably via regulating Wnt signaling pathway. This proposed project, for the first time, will elucidate the role of miR184 in the corneal neovascularization using in vivo specific model of corneal neovascularization and in vitro models of cell proliferation, migration and tube formation. We will also focus on the molecular mechanistic of miR184, such as targeted genes and related signaling pathway. This project will provide novel evidence that miR184 plays important role in the corneal neovascularization and serves as a new potential agent to treat corneal neovascularization related diseases.

MicroRNA是一类长度为21～25个核苷酸的内源性非编码蛋白的微小RNA，通过调节靶基因的基因表达，参与调控细胞增殖与分化、发育等生物学进程。研究表明miRNA-184在角膜中特异性高表达，目前尚无其在角膜中的作用，尤其是与角膜新生血管形成关系的相关报道。近期我们利用大鼠角膜缝线模型初步观察了miR-184对大鼠角膜新生血管形成的影响，结果表明该模型引起明显的角膜新生血管形成，同时miR-184表达显著降低及Wnt信号通路相关靶基因上调。因此我们提出假设miR-184可能通过作用Wnt信号通路等靶基因参与角膜新生血管的形成。本课题将深入探讨miR-184在体内抑制角膜新生血管形成的作用，在体外抑制血管内皮细胞增殖、迁移及管腔形成的能力，并研究其调节靶基因和信号通路等的分子作用机制。本课题将首次揭示miR-184和角膜新生血管的关系以及作为潜在的治疗角膜相关疾病手段提供新的实验依据。

角膜新生血管是常见的眼表病理改变，可造成患者严重的视力障碍直至失明。迄今为止，对角膜新生血管形成确切发病的分子机制仍不清楚。miRNA-184为长度21-25个核苷酸的内源性非编码蛋白的微小RNA，在角膜中特异性高表达，目前尚无与角膜新生血管形成关系的相关报道。本项目在前期利用大鼠角膜缝线模型初步观察了miR-184对大鼠角膜新生血管形成的影响，结果表明该模型引起明显的角膜新生血管形成，同时miR-184表达显著降低及Wnt信号通路相关靶基因上调。因此我们提出假设miR-184可能通过作用Wnt信号通路等靶基因参与角膜新生血管的形成。本课题深入探讨miRNA-184在体内抑制角膜新生血管形成的作用，在体外抑制血管内皮细胞增殖、迁移及管腔形成的能力，并阐明其调节靶基因和信号通路等的分子作用机制，为临床作为潜在的治疗角膜相关疾病手段提供新的实验依据。