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Targeting translational control as a novel way to treat inflammatory disease: The emerging role of MicroRNAs

机译：靶向翻译控制作为治疗炎性疾病的新方法：MicroRNA的新兴作用

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Chronic inflammatory diseases (e.g. asthma and chronic obstructive pulmonary disease) are leading causes of morbidity and mortality world-wide and effective treatments are limited. These disorders can often be attributed to abnormal immune responses to environmental stimuli and infections. Mechanisms leading to inflammation are complex, resulting from interactions of structural cells and activation of both the adaptive and innate arms of the immune system. The activation of structural and immune cells involves both temporary and permanent changes in gene expression in these cells, which underpin chronic inflammation and tissue dysfunction. miRNAs are small non-coding RNAs increasingly being recognized to play important roles in the post-transcriptional regulation of gene expression in mammalian cells by regulating translation. Individual miRNAs can exert their effects by directly inhibiting the translation or stability of multiple mRNAs simultaneously. Thus, the expression or blockade of function of a single miRNA (miR) can result in pronounced alterations in protein expression within a given cell. Dysregulation of miRNA expression may subsequently alter cellular function, and in certain situations predispose to disease. Our current understanding of the role of miRNA in the regulation of inflammatory disease (e.g. allergic diseases) remains limited. In this review, we provide an overview of the current understanding of miRNA biogenesis and function, the roles miRNA play in the regulation of immune cell function and their potential contribution to inflammatory diseases. We also highlight strategies to alter miRNA function for experimental or therapeutic gain, and discuss the potential utility and limitations of targeting these molecules as anti-inflammatory strategies.
机译：慢性炎性疾病（例如哮喘和慢性阻塞性肺疾病）是全世界发病率和死亡率的主要原因，并且有效治疗受到限制。这些疾病通常可归因于对环境刺激和感染的异常免疫反应。导致炎症的机制很复杂，这是由于结构细胞的相互作用以及免疫系统的适应性臂和先天性臂的激活所致。结构细胞和免疫细胞的激活涉及这些细胞中基因表达的暂时和永久变化，这是慢性炎症和组织功能障碍的基础。 miRNA是小的非编码RNA，人们越来越认识到，miRNA通过调节翻译在哺乳动物细胞基因表达的转录后调节中起重要作用。单个miRNA可以通过直接同时抑制多个mRNA的翻译或稳定性来发挥作用。因此，单个miRNA（miR）的功能表达或阻断可导致给定细胞内蛋白质表达的明显改变。 miRNA表达失调可能随后改变细胞功能，在某些情况下易患疾病。我们目前对miRNA在调节炎症性疾病（例如过敏性疾病）中的作用的了解仍然有限。在这篇综述中，我们概述了miRNA的生物发生和功能的当前理解，miRNA在调节免疫细胞功能中的作用及其对炎性疾病的潜在贡献。我们还重点介绍了改变miRNA功能以获得实验或治疗目的的策略，并讨论了靶向这些分子作为抗炎策略的潜在效用和局限性。

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