基于微阵列数据探讨金属硫蛋白在吸烟者气道的变化及其可能机制

Metallothionein expression and possible mechanism in smokers'airway based on microarray data

目的 探讨吸烟对气道金属硫蛋白(MT)表达的影响及其可能机制.方法 获取公共基因表达综合数据库(GEO)的微阵列矩阵数据并进行整合分析,以确定烟雾暴露后MT表达的变化趋势;同时使用miRDB数据库预测靶向16个MT的miRNA,CLUSTAL W软件对MT mRNA进行多序列比对.结果 急性吸烟刺激气道MT表达,慢性吸烟抑制气道MT表达.慢性吸烟者气道MT1、MT2、MT3表达与吸烟指数呈显著负相关,但其不影响MT4表达.MT1、MT2、MT3 mRNA序列包含“CTCCTGC”片段,可与hsa-miR-4722-5p种子区域匹配,而MT4 mRNA序列缺乏结合位点.结论 MT1、MT2、MT3和hsa-miR-4722-5p可能是减轻吸烟损伤和预防慢性阻塞性肺疾病(COPD)进展的潜在靶点.

Objective To investigate the effect of smoking on metallothionein(MT) expression and its possible mechanism in airway. Methods MT expression trend upon exposure to smoking was determined using microarray matrix data on Gene Expression Omnibus(GEO). The 16 MT-targeted mi RNAs and mRNAs were screened using miRDB database and aligned by CLUSTAL W software. Results Airway MT expression was upregulated by acute smoking but downregulated by chronic smoking. The smoking index was negatively correlated with airway MT1-3 other than MT4 expression in chronic smokers. The mRNA sequences of MT1-3 but not MT4 contained ‘CTCCTGC’ fragments, matching to the seed region of hsamiR-4722-5 p. Conclusion MT1-3 and hsa-miR-4722-5 p might be potential targets to reduce smoking injury and prevent progression of chronic obstructive pulmonary disease(COPD).