MicroRNAs-control of essential genes: Implications for pulmonary vascular disease.
MicroRNAs-control of essential genes: Implications for pulmonary vascular disease.
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DOI：
10.4103/2045-8932.87301
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发表时间：
2011-07
影响因子：
2.6
通讯作者：
Gerthoffer WT
中科院分区：
文献类型：
--
作者：
Joshi SR;McLendon JM;Comer BS;Gerthoffer WT
在正常的肺部发育过程中和肺部疾病中，肺部的结构细胞会进行适应以允许肺功能发生变化。成纤维细胞、肌成纤维细胞、平滑肌、上皮细胞和各种祖细胞都可以经历表型调节。在肺血管系统中，严重肺动脉高压中发生的闭塞性血管病变是多灶性、多克隆病变，其中含有推测已经历表型转变的细胞，导致增殖、细胞寿命或收缩性改变。负责这种细胞可塑性的过程中基因表达和蛋白质组成的动态变化尚未完全确定。分子生物学的进展表明，多种核糖核酸 (RNA) 相互协作，共同建立细胞中表达的一组蛋白质。编码信使核糖核酸 (mRNA) 和小非编码 RNA (miRNA) 均通过多个平行信号通路发挥作用，调节转录、mRNA 加工、mRNA 稳定性、翻译以及可能的蛋白质寿命。在描述一些血管组织中 miRNA 表达和 miRNA 功能的动态特征方面已经取得了快速进展。然而，通过 microRNA 介导的 mRNA 降解和翻译阻断导致的转录后基因沉默在肺血管系统中的定义尚不明确。综述了定义调节血管细胞表型的 miRNA 的最新进展，以说明小非编码 RNA 在肺动脉高压中的功能和治疗意义。
During normal lung development and in lung diseases structural cells in the lungs adapt to permit changes in lung function. Fibroblasts, myofibroblasts, smooth muscle, epithelial cells, and various progenitor cells can all undergo phenotypic modulation. In the pulmonary vasculature occlusive vascular lesions that occur in severe pulmonary arterial hypertension are multifocal, polyclonal lesions containing cells presumed to have undergone phenotypic transition resulting in altered proliferation, cell lifespan or contractility. Dynamic changes in gene expression and protein composition that underlie processes responsible for such cellular plasticity are not fully defined. Advances in molecular biology have shown that multiple classes of ribonucleic acid (RNA) collaborate to establish the set of proteins expressed in a cell. Both coding Messenger Ribonucleic acid (mRNA) and small noncoding RNAs (miRNA) act via multiple parallel signaling pathways to regulate transcription, mRNA processing, mRNA stability, translation and possibly protein lifespan. Rapid progress has been made in describing dynamic features of miRNA expression and miRNA function in some vascular tissues. However posttranscriptional gene silencing by microRNA-mediated mRNA degradation and translational blockade is not as well defined in the pulmonary vasculature. Recent progress in defining miRNAs that modulate vascular cell phenotypes is reviewed to illustrate both functional and therapeutic significance of small noncoding RNAs in pulmonary arterial hypertension.