Victoria Johnson Center for Obstructive Lung Diseases, Virginia Commonwealth University, Richmond, VA; Division of Respiratory Disease, Kanazawa Medical University, Ishikawa, Japan.
Victoria Johnson Center for Obstructive Lung Diseases, Virginia Commonwealth University, Richmond, VA; VU University Medical Center, Amsterdam, The Netherlands.
Chest. 2012 Sep;142(3):663-672. doi: 10.1378/chest.11-2746.
MicroRNAs (miRNAs) are small noncoding RNAs that silence target gene expression posttranscriptionally, and their impact on gene expression has been reported in various diseases. It has been reported that the expression of the hypoxia-inducible factor-1α (HIF-1α) is reduced and that of p53 is increased in lungs from patients with COPD. However, the role of miRNAs associated with these genes in lungs from patients with COPD is unknown.
Lung tissue samples from 55 patients were included in this study. Total RNA, miRNA, and protein were extracted from lung tissues and used for reverse transcriptase polymerase chain reaction and Western blot analysis. Cell culture experiments were performed using cultured human pulmonary microvascular endothelial cells (HPMVECs).
miR-34a and miR-199a-5p expressions were increased, and the phosphorylation of AKT was decreased in the lung tissue samples of patients with COPD. The miR-199a-5p expression was correlated with HIF-1α protein expression in the lungs of patients with COPD. Transfection of HPMVECs with the miR-199a-5p precursor gene decreased HIF-1α protein expression, and transfection with the miR-34a precursor gene increased miR-199a-5p expression.
These data suggest that miR-34a and miR-199a-5p contribute to the pathogenesis of COPD, and these miRNAs may also affect the HIF-1α-dependent lung structure maintenance program.
MicroRNAs（miRNAs）是一种小的非编码 RNA，可以在转录后沉默靶基因的表达，其在各种疾病中的基因表达影响已有报道。据报道，COPD 患者肺组织中的缺氧诱导因子-1α（HIF-1α）表达降低，p53 表达增加。然而，与这些基因相关的 miRNA 在 COPD 患者肺中的作用尚不清楚。
本研究纳入了 55 例患者的肺组织样本。从肺组织中提取总 RNA、miRNA 和蛋白质，用于逆转录聚合酶链反应和 Western blot 分析。通过培养的人肺微血管内皮细胞（HPMVEC）进行细胞培养实验。
COPD 患者肺组织中 miR-34a 和 miR-199a-5p 的表达增加，AKT 的磷酸化减少。COPD 患者肺组织中 miR-199a-5p 的表达与 HIF-1α 蛋白表达相关。HPMVECs 转染 miR-199a-5p 前体基因可降低 HIF-1α 蛋白表达，转染 miR-34a 前体基因可增加 miR-199a-5p 的表达。
这些数据表明，miR-34a 和 miR-199a-5p 参与 COPD 的发病机制，这些 miRNA 也可能影响 HIF-1α 依赖的肺结构维持程序。
