Divergent Roles of miR-3162-3p in Pulmonary Inflammation in Normal and Asthmatic Mice as well as Antagonism of miR-3162-3p in Asthma Treatment
Divergent Roles of miR-3162-3p in Pulmonary Inflammation in Normal and Asthmatic Mice as well as Antagonism of miR-3162-3p in Asthma Treatment
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miR-3162-3p 在正常小鼠和哮喘小鼠肺部炎症中的不同作用以及 miR-3162-3p 在哮喘治疗中的拮抗作用
DOI：
10.1159/000507250
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发表时间：
2020-07
影响因子：
2.8
通讯作者：
Zhang Xingliang
中科院分区：
文献类型：
--
作者：
Zhang Feng;Chen Yinhui;Liu Juman;Peng Xi;Mao Xiaoning;Lu Weihong;Wu Ruijian;Huang Binglong;Bao Yanmin;Ma Lian;Huang Yuge;Zhang Xingliang
与糖皮质激素作为哮喘的主要治疗方法相比，MicroRNA (miRNA) 模拟物或拮抗剂在哮喘治疗方面具有广阔的前景。但 miRNA 在调节哮喘炎症中的作用尚不清楚。我们之前报道哮喘儿童外周血中miR-3162-3p较健康儿童明显上调。本研究旨在阐明miR-3162-3p在正常小鼠和哮喘小鼠肺部炎症中的作用，并初步探讨miR-3162-3p antagomir在哮喘治疗中的潜力。无创全身体积描记器测量气道反应性。 qRT-PCR和Western blot均用于检测miRNA、mRNA或蛋白质的表达。通过血小板计数和赖特染色对支气管肺泡灌洗液中的细胞进行计数。分别通过苏木精和曙红以及高碘酸希夫染色来鉴定炎症浸润和粘液分泌。通过ELISA检测肺中的细胞因子。腹腔内给予正常小鼠的miR-3162-3p模拟物降低了肺部的β-连环蛋白水平，而没有明显改变肺部组织学和细胞因子水平。在卵清蛋白诱导的哮喘小鼠中拮抗 miR-3162-3p 可有效缓解哮喘的典型特征，如气道高反应性、气道炎症和 Th1/Th2 细胞因子失衡，并同时挽救总的和活性的 β-catenin 表达。总的来说，我们发现 miR-3162-3p 在正常小鼠和哮喘小鼠肺部炎症中的不同作用。 miR-3162-3p antagomir 的抗炎作用与糖皮质激素治疗相当。我们的研究有助于了解 miRNA 对哮喘发病机制的贡献。
MicroRNA (miRNA) mimics or antagomirs hold great promise for asthma treatment compared with glucocorticoids as mainstay therapy for asthma. But the role of miRNA in regulating asthmatic inflammation is largely unclear. We previously reported that miR-3162-3p in the peripheral blood of children with asthma was obviously upregulated compared to that in healthy children. This study aimed to elucidate the role of miR-3162-3p in pulmonary inflammation in normal and asthmatic mice as well as preliminarily explore the potential of miR-3162-3p antagomir in asthma treatment. A noninvasive whole-body plethysmograph measured airway responsiveness. Both qRT-PCR and Western blot were used to detect the expression of miRNA, mRNA, or protein. Cells in bronchoalveolar lavage fluid were counted by platelet counting and Wright’s staining. Inflammatory infiltration and mucus secretion were identified by hematoxylin and eosin and periodic acid-Schiff staining, respectively. Cytokines in the lungs were detected by ELISA. The miR-3162-3p mimic intraperitoneally administered to normal mice decreased β-catenin levels in the lungs without obviously altering the lung histology and cytokine levels. Antagonizing miR-3162-3p in ovalbumin-induced asthmatic mice effectively alleviated the typical features of asthma, such as airway hyperresponsiveness, airway inflammation, and Th1/Th2 cytokine imbalance, and concomitantly rescued the total and active β-catenin expression. Collectively, we discovered divergent roles of miR-3162-3p in lung inflammation between normal and asthmatic mice. The anti-inflammatory effects of the miR-3162-3p antagomir were comparable to those of glucocorticoid treatment. Our study helped in understanding the contribution of miRNAs to the pathogenesis of asthma.
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DOI：
10.4049/jimmunol.1101235
发表时间：
2011-09-15
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Lu TX;Hartner J;Lim EJ;Fabry V;Mingler MK;Cole ET;Orkin SH;Aronow BJ;Rothenberg ME
通讯作者：
Rothenberg ME
环境 PM2.5 通过活性氧损伤层状体对表面活性剂蛋白 A 的表达和运输产生不利影响
影响因子：
3.5
作者：
Peng, Juanjuan;Zhang, Lingli;Zhang, Xingliang
通讯作者：
Zhang, Xingliang
影响因子：
4.4
作者：
Reuter, Sebastian;Martin, Helen;Taube, Christian
通讯作者：
Taube, Christian
影响因子：
3.3
作者：
Amit Sharma;Manish Kumar;T. Ahmad;U. Mabalirajan;J. Aich;A. Agrawal;B. Ghosh
通讯作者：
Amit Sharma;Manish Kumar;T. Ahmad;U. Mabalirajan;J. Aich;A. Agrawal;B. Ghosh
环境 PM2.5 暴露会加剧先前过敏小鼠的过敏性哮喘严重程度
影响因子：
1.9
作者：
Zhang, Xingliang;Zhong, Wenqing;Tan, Jianxin
通讯作者：
Tan, Jianxin