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MicroRNA-7188-5p 和 miR-7235 调控实验性自身免疫性脑脊髓炎小鼠模型中的多发性硬化症。

MicroRNA-7188-5p and miR-7235 regulates Multiple sclerosis in an experimental mouse model.

机构信息

Biological Sciences Department, College of Science, King Faisal University, Hofouf, Alhasa, 31982, Saudi Arabia; Pondicherry Centre for Biological Science and Educational Trust, Pondicherry, 605005, India.

Biological Sciences Department, College of Science, King Faisal University, Hofouf, Alhasa, 31982, Saudi Arabia.

出版信息

Mol Immunol. 2021 Nov;139:157-167. doi: 10.1016/j.molimm.2021.07.002. Epub 2021 Sep 17.

Abstract

The short non-coding microRNAs (miRNAs) have emerged as reliable modulators of various pathological conditions including autoimmune diseases in mammals. The current study, aims to identify new potential differential expressed miRNAs and their downstream mRNA targets of the autoimmune disease, Multiple sclerosis (MS). The study identifies a new set of miRNA(s) that are probably implicated in MS using computational tools. The study further carried-out different in vivo and in vitro experiments to check these identified miRNAs could be role in as therapeutic and prognostic applications. Preliminary insilico screening revealed that miR-659-3p, miR-659-5p, miR-684, miR-3607-3p, miR-3607-5p, miR-3682-3p, miR-3682-5p miR-4647, miR-7188-3p, miR-7188-5p and miR-7235 are specifically elevated in the secondary lymphoid cells of EAE mice. In addition, expression of the downstream target mRNA of these miRNAs such as FXBO33, SGMS-1, ZDHHC-9, GABRA-3, NRXN-2 were reciprocal to miRNA expression in lymphoid cells. These confirmed by applying the mimic and silencing miRNA models, suggesting new inflammatory target genes of these promising miRNA markers. The in vivo adoptive transfer model revealed that the suppression of miRNA-7188-5p and miR-7235 changed the pattern of astrocytes and CNS pathophysiology. The current study opens a new miRNA and their mRNA targets in MS disease. The absence of miRNA-7188-5p and miR-7235 enhanced the disease alleviation, confirms the regulatory effect of these targets. These optimized results highlights new set of miRNA's with therapeutic potential in experimental MS. Further studies are required to confirm these miRNA as therapeutic biomarker.

摘要

短的非编码 microRNAs(miRNAs)已成为哺乳动物各种病理状况(包括自身免疫性疾病)可靠的调节剂。本研究旨在使用计算工具鉴定自身免疫性疾病多发性硬化症(MS)的新的潜在差异表达 miRNA 及其下游 mRNA 靶标。该研究使用计算工具鉴定了一组可能与 MS 相关的新 miRNA。该研究进一步进行了不同的体内和体外实验,以检查这些鉴定的 miRNA 是否可以作为治疗和预后应用。初步的计算机筛选显示,miR-659-3p、miR-659-5p、miR-684、miR-3607-3p、miR-3607-5p、miR-3682-3p、miR-3682-5p、miR-4647、miR-7188-3p、miR-7188-5p 和 miR-7235 在 EAE 小鼠的次级淋巴器官中特异性升高。此外,这些 miRNA 的下游靶 mRNA 的表达,如 FXBO33、SGMS-1、ZDHHC-9、GABRA-3、NRXN-2,与淋巴细胞中 miRNA 的表达呈反相关。通过应用模拟物和沉默 miRNA 模型,证实了这些有前途的 miRNA 标志物的新炎症靶基因。体内过继转移模型表明,miR-7188-5p 和 miR-7235 的抑制改变了星形胶质细胞和中枢神经系统病理生理学的模式。本研究在 MS 疾病中开辟了新的 miRNA 及其 mRNA 靶标。miR-7188-5p 和 miR-7235 的缺失增强了疾病缓解,证实了这些靶标的调节作用。这些优化结果突出了具有实验性 MS 治疗潜力的新 miRNA 集。需要进一步研究来确认这些 miRNA 作为治疗性生物标志物。

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