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长非编码 RNA 揭示儿童哮喘中的重要通路:未来展望。

Long non coding RNAs reveal important pathways in childhood asthma: a future perspective.

机构信息

Department of Anesthesiology, Rasoul-Akram Medical Center, Iran University of Medical Sciences (IUMS), Tehran, Iran.

Arak University of Medical Sciences, Arak, Iran.

出版信息

J Mol Histol. 2023 Aug;54(4):257-269. doi: 10.1007/s10735-023-10131-y. Epub 2023 Aug 4.

Abstract

Asthma is a long-term inflammatory disease of the airways of the lungs refers changes that occur in conjunction with, or as a result of, chronic airway inflammation. Airway remodeling the subsequent of inflammation constitutes cellular and extracellular matrix changes in the wall airways, epithelial-to-mesenchymal-transition and airway smooth muscle cell proliferation. Diseases often begin in childhood and despite extensive research, causative pathogenic mechanisms still remain unclear. Transcriptome analysis of childhood asthma reveals distinct gene expression profiles of Long noncoding RNAs which have been reported to play a central regulatory role in various aspects of pathogenesis, clinical course and treatment of asthma. We briefly review current understanding of lnc-RNA dysregulation in children with asthma, focusing on their complex role in the inflammation, cell proliferation and remodeling of airway to guide future researches. We found that the lnc-RNAs increases activity of several oncogenes such c-Myc, Akt, and ERK and various signaling pathways such as MAPK (PI3K, Ras, JNK and p38), NF-κB and Wnt and crosstalk between these pathways by TGFβ, β-catenin, ERK and SKP2. Moreover, two different signal transduction pathways, Wnt and Notch1, can be activated by two lnc-RNAs through sponging the same miRNA for exacerbation cell proliferation.

摘要

哮喘是一种肺部气道的慢性炎症性疾病,是气道炎症伴随或作为其结果发生的改变。气道重塑是炎症后的细胞和细胞外基质在气道壁的改变、上皮-间充质转化和气道平滑肌细胞增殖。该疾病通常在儿童时期开始,尽管进行了广泛的研究,但致病机制的病因仍不清楚。儿童哮喘的转录组分析揭示了长非编码 RNA 的独特基因表达谱,据报道,长非编码 RNA 在哮喘的发病机制、临床过程和治疗的各个方面发挥着核心调节作用。我们简要回顾了目前对儿童哮喘中 lnc-RNA 失调的理解,重点关注它们在气道炎症、细胞增殖和重塑中的复杂作用,以指导未来的研究。我们发现,lnc-RNAs 增加了几个癌基因的活性,如 c-Myc、Akt 和 ERK,以及各种信号通路,如 MAPK(PI3K、Ras、JNK 和 p38)、NF-κB 和 Wnt,以及 TGFβ、β-catenin、ERK 和 SKP2 之间的这些途径的串扰。此外,两条不同的信号转导途径,Wnt 和 Notch1,可以通过两种 lnc-RNAs 来激活,通过海绵吸附相同的 miRNA 来促进细胞增殖。

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