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由慢病毒载体递送的针对微小RNA-155的小干扰RNA可减轻过敏性哮喘小鼠模型中的哮喘特征。

Small interfering RNA directed against microRNA-155 delivered by a lentiviral vector attenuates asthmatic features in a mouse model of allergic asthma.

作者信息

Chen Huilong, Xu Xiangqin, Cheng Sheng, Xu Yuzhu, Xuefei Qi, Cao Yong, Xie Jungang, Wang Cong-Yi, Xu Yongjian, Xiong Weining

机构信息

Department of Respiratory and Critical Care Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, P.R. China.

Center for Biomedical Research, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, P.R. China.

出版信息

Exp Ther Med. 2017 Nov;14(5):4391-4396. doi: 10.3892/etm.2017.5093. Epub 2017 Sep 1.

Abstract

Asthma is a chronic T helper type 2 (Th2) cell-mediated inflammatory disease characterized by airway hyperresponsiveness (AHR) and airway inflammation. Although the majority of patients with asthma can achieve a good level of control with existing treatments, asthma runs a chronic course and the effectiveness of current treatment is not satisfactory for certain patients. MicroRNAs (miRNAs) are short noncoding RNAs that suppress gene expression at the post-transcriptional level; their role in regulating allergic inflammation remains largely unknown. The present study aimed to explore the role of miRNA-155 in the pathogenesis of asthma and its potential as a target for treatment. The expression of miRNA-155 increased in ovalbumin-sensitized and challenged mice compared with control mice, and lentiviral vector-delivered small interfering (si)RNA targeting miRNA-155 resulted in reduced AHR, airway inflammation and Th2 cytokine production. The data from the present study indicate that miRNA-155 serves an important role in the pathogenesis of asthma, and that lentiviral vector-delivered siRNA targeting miRNA-155 may serve as a novel approach for the treatment of allergic asthma.

摘要

哮喘是一种慢性2型辅助性T细胞(Th2)介导的炎症性疾病,其特征为气道高反应性(AHR)和气道炎症。尽管大多数哮喘患者通过现有治疗可达到较好的控制水平,但哮喘呈慢性病程,且当前治疗对某些患者的疗效并不令人满意。微小RNA(miRNA)是短链非编码RNA,可在转录后水平抑制基因表达;其在调节过敏性炎症中的作用仍 largely unknown。本研究旨在探讨miRNA-155在哮喘发病机制中的作用及其作为治疗靶点的潜力。与对照小鼠相比,卵清蛋白致敏和激发的小鼠中miRNA-155的表达增加,且慢病毒载体递送的靶向miRNA-155的小干扰(si)RNA导致AHR降低、气道炎症减轻和Th2细胞因子产生减少。本研究的数据表明,miRNA-155在哮喘发病机制中起重要作用,且慢病毒载体递送的靶向miRNA-155的siRNA可能作为治疗过敏性哮喘的一种新方法。

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