长链非编码RNA uc.77在百草枯致肺纤维化中的作用与机制

项目名称： 长链非编码RNA uc.77在百草枯致肺纤维化中的作用与机制

项目编号： No.81201459

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： 孙昊

作者单位： 南京医科大学

项目金额： 23万元

中文摘要： 百草枯中毒可引起严重肺纤维化，导致呼吸衰竭而死亡，已成为急诊医学中有待攻克的难题。uc.77是我们采用芯片技术筛选小鼠正常肺组织、百草枯致纤维化肺组织差异非编码RNA时发现的、高表达于纤维化肺组织的lncRNA。前期实验发现抑制uc.77表达可缓解百草枯诱导的肺纤维化作用，并初步证实ZEB2是uc.77可能的下游靶基因，而文献报道ZEB2参与肺纤维化机制，提示uc.77可能通过调节ZEB2机制在百草枯致肺纤维化中发挥作用。迄今国内外尚无lncRNA在肺纤维化形成机制中的研究，因此本研究有源头创新性。拟采用过表达与敲低策略，明确uc.77在百草枯致肺纤维化中的功能，并以ZEB2为研究线索，分析uc.77参与百草枯致肺纤维化可能的作用机制，从而为百草枯致肺纤维化的干预或逆转提供新的靶标。

中文关键词： 百草枯；肺纤维化；长链非编码RNA；上皮-间充质细胞转分化；uc.77

英文摘要： Paraquat poisoning can cause severe pulmonary fibrosis, respiratory failure and death are remains a challenge in emergency medicine. We used non-coding RNA microarray to compare tissues from normal mouse lung and paraquat-induced pulmonary fibrosis and identified uc.77 as a long non-coding RNA (lncRNA) that is highly expressed in pulmonary fibrosis tissues. Preliminary study found that inhibition of uc.77 could alleviate paraquat-induced pulmonary fibrosis and confirmed ZEB2 as a potential uc.77 target gene. Since ZEB2 was reported to be important in the mechanism of pulmonary fibrosis, our study suggests that uc.77 could promote paraquat-induced pulmonary fibrosis through regulating the expression of ZEB2. As currently there is few study on the role of lncRNA in pulmonary fibrosis, our research will provide important novel insights.We plan to use overexpression and knockdown approaches to clarify the function of uc.77 in paraquat-induced pulmonary fibrosis and study its mechanism of action with ZEB2 as a candidate. This study will reveal potential targets for the intervention and treatment of paraquat-induced pulmonary fibrosis.

英文关键词： Paraquat；Pulmonary Fibrosis；Long non-coding RNA；Epithelial–mesenchymal transition；uc.77