转录因子ETS1与LEF1协同下调在早产儿支气管肺发育不良疾病中的研究

The synergistic effect of transcription factor ETS1, LEF1 in bronchopulmonary dysplasia development

目的探讨血管新生相关转录因子ETS1与LEF1在早产儿支气管肺发育不良(BPD)发生、发展中的作用。方法对来自Gene Expression Omnibus公共数据库的早产儿血液样本表达谱芯片数据进行分析,比较ETS1、LEF1和基质金属蛋白酶基因(MMPs)在EPD与非BPD以及不同疾病严重程度BPD中的表达情况;并分析这些基因表达的相关性°结果与非BPD组早产儿相比.转录因子ETS1与LEF1表达量在BPD早产儿中均显著降低.且疾病越严重表达量越低.出生周龄越大表达量越高。ETS1与LEF1表达有相关性(r=0.921, PV0.001)。MMPK MMP2. MMP7以及MMP13在早产儿中表达量均较低.MMP9表达量随BPD严重程度增加而升高。结论在早产儿中转录因子ETS1与LEF1表达下调与BPD疾病具有相关性。BPD发病机制可能是ETS1与LEF1协同下调表达以及早产儿中低水平表达的MMPs共同阻碍了血管内皮细胞的增殖和迁移.进而导致了 BPD的病变基础即肺泡和肺血管发育不良.

Objective The aim of this study was to investigate the function of angiogenesis related transcriptional factors ETS1 , LEF1 in development of bronchopulm on ary dysplasia. Methods A gene expression dataset of preterm infant published in Gene Expression Omnibus database. The expression values of ETS1, LEF1 and matrix metalloproteinase ( MMPs) in BPD and no BPD samples were compared and the correlation analysis of these genes was performed. The possible mechanism of ETS1 and LEF1 to participate in the development of BPD via the regulation of MMPs was discussed. Results Expression levels of ETS1 and LEF1 were significantly downregulated in BPI) samples and related with the severity of BPD and its complication retinopathy of prematurity. The expression of ETS1 and LEF1 had a good fitting rate ( r =0.921, P <0.001). Conclusions The down regulation of ETS1 and LEF1 at least in part related with BPD development. The potential mechanism would be synergism downregulation of ETS1 and LEF1 attenuated the expression and function of MMPs, which may affect the migration and proliferation of vascular endothelial cell. It also leads to the lesion basis of BPI), the dysplasia of alveoli and pulm on ary vessels.