Elevated microRNA-135a is associated with pulmonary arterial hypertension in experimental mouse model.
Elevated microRNA-135a is associated with pulmonary arterial hypertension in experimental mouse model.
复制标题
DOI：
10.18632/oncotarget.16011
复制
发表时间：
2017-05-30
期刊：
影响因子：
--
通讯作者：
Park SH
中科院分区：
文献类型：
--
作者：
Lee HW;Park SH
肺动脉高压(PAH)的发病机制复杂，病因多样，但其发病的分子途径仍不清楚。在这项研究中，我们研究了小鼠暴露于组合 Th2 抗原（卵清蛋白，OVA）和城市颗粒物 (PM) 引起 PAH 的表观遗传变化。为了解决这个问题，我们重点关注与 microRNA (miR)-135a 相关的表观遗传机制。我们发现，在该实验性PAH小鼠模型中，miR-135a水平显着升高，而作为miR-135a靶标的II型骨形态发生蛋白受体（BMPR2）的水平显着降低。因此，为了评估 miR-135a 的作用，我们将 AntagomiR-135a 注射到该小鼠模型中。与注射混杂 miRNA 的对照小鼠相比，注射 AntagomiR-135a 的小鼠右心室收缩压 (RVSP) 降低、右心室肥厚 (RVH) 以及肺动脉严重增厚的百分比降低。与对照小鼠相比，注射 AntagomiR-135a 的小鼠中 BMPR2 的 mRNA 和蛋白表达均得到恢复。我们的研究了解 miR-135a 是否可以作为有助于控制 PAH 的生物标志物。阻断 miR-135a 可能会带来新的治疗方式，以减轻因暴露于 Th2 抗原和城市空气污染而引起的 PAH 恶化。
Multiple causes are associated with the complex mechanism of pathogenesis of pulmonary arterial hypertension (PAH), but the molecular pathway in the pathogenesis of PAH is still insufficiently understood. In this study, we investigated epigenetic changes that cause PAH induced by exposure to combined Th2 antigen (Ovalbumin, OVA) and urban particulate matter (PM) in mice. To address that, we focused on the epigenetic mechanism, linked to microRNA (miR)-135a. We found that miR-135a levels were significantly increased, and levels of bone morphogenetic protein receptor type II (BMPR2) which is the target of miR-135a, were significantly decreased in this experimental PAH mouse model. Therefore to evaluate the role of miR-135a, we injected AntagomiR-135a into this mouse model. AntagomiR-135a injected mice showed decreased right ventricular systolic pressures (RVSPs), right ventricular hypertrophy (RVH), and the percentage of severely thickened pulmonary arteries compared to control scrambled miRNA injected mice. Both mRNA and protein expression of BMPR2 were recovered in the AntagomiR-135a injected mice compared to control mice. Our study understands if miR-135a could serve as a biomarker helping to manage PAH. The blocking of miR-135a could lead to new therapeutic modalities to alleviate exacerbation of PAH caused by exposure to Th2 antigen and urban air pollution.