靶向调控PAI-1的lncRNAs在COPD肺泡上皮细胞凋亡中的作用及机制研究

Excessive apoptosis of alveolar cells are associated with the pathogenesis of COPD. Long noncoding RNA are generally considered as non-protein coding transcripts longer than 200 nucleotides，and related to the progress of various diseases by regulate the expression of mRNA. In our previously study，plasminogen activator inhibitor-1 （PAI-1）showed decreased expression on COPD alveolar epithelium，and negative related to alveolar apoptosis index. LncRNA changed in COPD sample compared to controls by the detection of lncRNA microarray screen. Some of the changed lncRNAs in COPD are related to PAI-1 expression when analyzed by bioinformatics. These results suggest that lncRNAs may participate alveolar apoptosis through regulate PAI-1 mRNA expression. To test our hypothesis, we plan to: 1.Verify the regulation effect of lncRNAs on PAI-1; 2. Clarify that lncRNAs participate alveolar apoptosis by regulate PAI-1 expression 3. Explore the possible signal mechanism of alveolar apoptosis induced by PAI-1 related lncRNAs.These will further help us understand the pathogenesis of COPD, and will shed new lights on prevention and treatment of COPD

细胞凋亡是COPD肺气肿病理形成的重要机制。长链非编码RNA（lncRNA）是一类新发现的长度超过200nt的非编码RNA，可以通过调控mRNA的表达参与疾病的发生。我们的前期研究发现：尿激酶型纤溶酶原抑制剂-1（PAI-1）在COPD患者肺泡上皮细胞表达降低，且PAI-1在体内外的表达水平与肺泡上皮细胞凋亡密切相关；高通量lncRNA芯片检测及生物信息学分析结果显示COPD的异常lncRNA表达谱中，有部分可以靶向调控PAI-1的lncRNAs。这些研究结果强烈提示lncRNAs可能通过调控PAI-1表达参与COPD肺泡上皮细胞凋亡。本研究试图：1.筛选并验证对PAI-1有调控作用的lncRNAs；2.明确lncRNAs通过调控PAI-1参与COPD肺泡上皮细胞凋亡的作用；3.阐明lncRNAs通过PAI-1参与COPD肺泡上皮细胞凋亡的信号转导机制，为COPD的防治提出新的靶点。