miR-21 regulates chronic hypoxia-induced pulmonary vascular remodeling
miR-21 regulates chronic hypoxia-induced pulmonary vascular remodeling
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DOI：
10.1152/ajplung.00316.2011
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发表时间：
2012-03-01
影响因子：
4.9
通讯作者：
Liu, Gang
中科院分区：
文献类型：
--
作者：
Yang, Shanzhong;Banerjee, Sami;Liu, Gang
杨S，班纳吉S，德弗雷塔斯A，崔H，谢N，亚伯拉罕E，刘G. miR-21调节慢性缺氧诱导的肺血管重构美国生理学杂志肺细胞分子生理学302：L521-L529，2012年。首次发表于2012年1月6日; doi：10.1152/ajplung.00316.2011。慢性缺氧引起肺血管重构，导致肺动脉高压（PH）和右心室（RV）肥大。microRNA（miRNA）的异常表达与许多病理生理过程密切相关。然而，miRNAs在慢性缺氧诱导的肺血管重构和PH中的作用尚未得到很好的表征。在这项研究中，我们发现低氧暴露小鼠肺远端小动脉中miR-21的表达增加。假定的miR-21靶点，包括骨形态发生蛋白受体（BMPR 2），WWP 1，SATB 1和YOD 1，在缺氧暴露小鼠的肺和过表达miR-21的人肺动脉平滑肌细胞（PASMC）中下调。我们发现，无论是在缺氧暴露之前还是之后，隔离miR-21都可以减少慢性缺氧诱导的PH并减弱缺氧诱导的肺血管重塑，这可能是通过缓解缺氧暴露小鼠肺中miR-21靶点的抑制表达。miR-21的过表达增强了人PASMCs的体外增殖，而miR-21的下调减弱了细胞增殖相关蛋白的表达，如增殖细胞核抗原、细胞周期蛋白D1和Bcl-xL。我们的数据表明，miR-21在慢性缺氧诱导的肺血管重构的发病机制中起着重要作用，也表明miR-21是治疗慢性缺氧相关肺部疾病的新型疗法的潜在靶点。
Yang S, Banerjee S, de Freitas A, Cui H, Xie N, Abraham E, Liu G. miR-21 regulates chronic hypoxia-induced pulmonary vascular remodeling. Am J Physiol Lung Cell Mol Physiol 302: L521-L529, 2012. First published January 6, 2012; doi:10.1152/ajplung.00316.2011.-Chronic hypoxia causes pulmonary vascular remodeling leading to pulmonary hypertension (PH) and right ventricle (RV) hypertrophy. Aberrant expression of microRNA (miRNA) is closely associated with a number of pathophysiologic processes. However, the role of miRNAs in chronic hypoxia-induced pulmonary vascular remodeling and PH has not been well characterized. In this study, we found increased expression of miR-21 in distal small arteries in the lungs of hypoxia-exposed mice. Putative miR-21 targets, including bone morphogenetic protein receptor (BMPR2), WWP1, SATB1, and YOD1, were downregulated in the lungs of hypoxia-exposed mice and in human pulmonary artery smooth muscle cells (PASMCs) over-expressing miR-21. We found that sequestration of miR-21, either before or after hypoxia exposure, diminished chronic hypoxia-induced PH and attenuated hypoxia-induced pulmonary vascular remodeling, likely through relieving the suppressed expression of miR-21 targets in the lungs of hypoxia-exposed mice. Overexpression of miR-21 enhanced, whereas downregulation of miR-21 diminished, the proliferation of human PASMCs in vitro and the expression of cell proliferation associated proteins, such as proliferating cell nuclear antigen, cyclin D1, and Bcl-xL. Our data suggest that miR-21 plays an important role in the pathogenesis of chronic hypoxia-induced pulmonary vascular remodeling and also suggest that miR-21 is a potential target for novel therapeutics to treat chronic hypoxia associated pulmonary diseases.