lncRNA介导的SIRT1信号网络调控的Ⅱ型肺泡上皮细胞衰老在慢性阻塞性肺疾病中的作用机制研究

项目名称： lncRNA介导的SIRT1信号网络调控的Ⅱ型肺泡上皮细胞衰老在慢性阻塞性肺疾病中的作用机制研究

项目编号： No.81470241

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： 李亚清

作者单位： 杭州医学院

项目金额： 75万元

中文摘要： 修复损伤的肺组织、使丢失的肺泡再生是慢性阻塞性肺疾病(COPD)治疗中的关键所在。II型肺泡上皮细胞(AECII)是I型肺泡上皮细胞的祖细胞，在维持肺泡正常结构和功能中起重要作用。我们前期研究发现羊水间充质干细胞(AF-MSC)在肺气肿大鼠肺组织内定向分化为AECII、使肺泡数量增加。但其分化纯度及致瘤风险等问题仍未解决，外源性干细胞治疗COPD仍面临重重困难。因此，恢复内源性干细胞功能以促进肺组织修复值得进一步研究。过早细胞衰老直接影响肺部祖细胞功能，导致干细胞池耗竭及肺组织损伤。SIRT1信号通路在细胞衰老中起着至关重要作用，长非编码RNA（lncRNA）参与细胞衰老调控过程。因此，本项目将应用lncRNA芯片、真核表达载体转染、基因敲除等技术研究肺部关键性lncRNA介导的SIRT1信号网络在AECII衰老中的调控作用，揭示促进COPD进展的细胞衰老机制，为COPD治疗提供新的靶点。

中文关键词： 慢性阻塞性肺疾病；II型肺泡上皮细胞；Sirtuins；细胞衰老；长非编码RNA

英文摘要： The key to treat chronic obstructive pulmonary disease (COPD) is how to repair damaged lung tissue and regenerate the lost alveoli. As the progenitors of type I alveolar epithelial cells, type II alveolar epithelial cells (AECII) play important roles in the maintenance of alveoli structure and function.Our previous study indicated that amniotic fluid-derived mesenchymal stem cells (AF-MSC) can differentiate into AECII in the lungs of the rats with emphysema, and then repair the damaged alveoli. However,there are many problems including in the purity and tumor risk in the differentiation that have not been solved. There are still many difficulties in treating COPD using exogenous stem cells. Therefore, it is useful to study how to repair the damaged lung tissue by the recovery of endogenous stem cells. Premature cellular senescence directly affects the lung progenitor cell function, causing the depletion of stem cells and lung tissue destruction. SIRT1 signaling plays a crucial role in cellular senescence. Long non-coding RNA (lncRNA) directly plays important regulatory roles in the course.Thus, in the present study, lncRNA chip, eukaryotic expression vector transfection, and gene knockout technology will be used to study the mechanisms of type II alveolar epithelial cell senescence regulated by lncRNA-mediated SIRT1 signaling networks in chronic obstructive pulmonary disease and reveal the roles of cellular senescence in the progression of COPD, which will provide new therapeutic targets for COPD.

英文关键词： chronic obstructive pulmonary disease;type II alveolar epithelial cells;Sirtuins;cellular senescence;long non-coding RNA