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炎症性肺病中的 microRNAs——主调控因子还是靶向治疗?

MicroRNAs in inflammatory lung disease--master regulators or target practice?

机构信息

Respiratory Research Division, Department of Medicine, Royal College of Surgeons in Ireland, Beaumont Hospital, Dublin, Ireland.

出版信息

Respir Res. 2010 Oct 28;11(1):148. doi: 10.1186/1465-9921-11-148.

Abstract

MicroRNAs (miRNAs) have emerged as a class of regulatory RNAs with immense significance in numerous biological processes. When aberrantly expressed miRNAs have been shown to play a role in the pathogenesis of several disease states. Extensive research has explored miRNA involvement in the development and fate of immune cells and in both the innate and adaptive immune responses whereby strong evidence links miRNA expression to signalling pathways and receptors with critical roles in the inflammatory response such as NF-κB and the toll-like receptors, respectively. Recent studies have revealed that unique miRNA expression profiles exist in inflammatory lung diseases such as cystic fibrosis, chronic obstructive pulmonary disease, asthma, idiopathic pulmonary fibrosis and lung cancer. Evaluation of the global expression of miRNAs provides a unique opportunity to identify important target gene sets regulating susceptibility and response to infection and treatment, and control of inflammation in chronic airway disorders. Over 800 human miRNAs have been discovered to date, however the biological function of the majority remains to be uncovered. Understanding the role that miRNAs play in the modulation of gene expression leading to sustained chronic pulmonary inflammation is important for the development of new therapies which focus on prevention of disease progression rather than symptom relief. Here we discuss the current understanding of miRNA involvement in innate immunity, specifically in LPS/TLR4 signalling and in the progression of the chronic inflammatory lung diseases cystic fibrosis, COPD and asthma. miRNA in lung cancer and IPF are also reviewed.

摘要

微小 RNA(miRNAs)已成为一类具有重要意义的调节性 RNA,在许多生物学过程中发挥着重要作用。当异常表达的 miRNAs 被证明在几种疾病状态的发病机制中起作用时。广泛的研究探索了 miRNA 在免疫细胞的发育和命运以及先天和适应性免疫反应中的作用,强有力的证据将 miRNA 表达与信号通路和受体联系起来,这些信号通路和受体在炎症反应中具有重要作用,如 NF-κB 和 Toll 样受体。最近的研究表明,在炎症性肺部疾病(如囊性纤维化、慢性阻塞性肺疾病、哮喘、特发性肺纤维化和肺癌)中存在独特的 miRNA 表达谱。评估 miRNAs 的全局表达提供了一个独特的机会,可以识别调节易感性和对感染和治疗反应以及慢性气道疾病炎症控制的重要靶基因集。迄今为止,已经发现了超过 800 个人类 miRNAs,但大多数 miRNA 的生物学功能仍有待发现。了解 miRNAs 在调节基因表达导致持续慢性肺部炎症中的作用对于开发新的治疗方法非常重要,这些方法侧重于预防疾病进展,而不是缓解症状。在这里,我们讨论了 miRNA 在内生免疫中的作用,特别是在 LPS/TLR4 信号转导和慢性炎症性肺部疾病(囊性纤维化、COPD 和哮喘)的进展中的作用。还回顾了肺癌和特发性肺纤维化中的 miRNA。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8007/2984500/b41f7c1f2d0f/1465-9921-11-148-1.jpg

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