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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.
International Archives of Allergy and Immunology ( IF 2.8 ) Pub Date : 2020-07-01 , DOI: 10.1159/000507250
Juman Liu 1 , Yinhui Chen 1 , Feng Zhang 2 , Xi Peng 1 , Xiaoning Mao 3 , Weihong Lu 4 , Ruijian Wu 1 , Binglong Huang 1 , Yanmin Bao 5 , Lian Ma 6, 7 , Yuge Huang 8 , Xingliang Zhang 6, 9
Affiliation  

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.
Int Arch Allergy Immunol


中文翻译:

miR-3162-3p在正常和哮喘小鼠肺炎症中的不同作用,以及miR-3162-3p在哮喘治疗中的拮抗作用。

与糖皮质激素作为哮喘的主要治疗方法相比,MicroRNA(miRNA)模拟物或拟抑素在哮喘治疗方面具有广阔的前景。但是,miRNA在调节哮喘炎症中的作用尚不清楚。我们先前曾报道,与健康儿童相比,哮喘儿童外周血中的miR-3162-3p明显上调。这项研究旨在阐明miR-3162-3p在正常和哮喘小鼠的肺部炎症中的作用,并初步探索miR-3162-3p的潜力安塔哥米尔治疗哮喘。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氏染色计数支气管肺泡灌洗液中的细胞。分别通过苏木精和曙红和高碘酸-希夫(Schiff)染色鉴定炎性浸润和粘液分泌。通过ELISA检测肺中的细胞因子。腹膜内给予正常小鼠的miR-3162-3p模拟物可降低肺中的β-catenin水平,而不会明显改变肺组织学和细胞因子水平。拮抗miR-3162-3p卵清蛋白诱导的哮喘小鼠体内的β-连环蛋白可有效缓解哮喘的典型特征,例如气道高反应性,气道炎症和Th1 / Th2细胞因子失衡,并同时挽救了β-catenin的总表达和活性。集体地,我们发现在正常小鼠和哮喘小鼠之间,miR-3162-3p在肺部炎症中的作用不同。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在哮喘发病中的作用。
Int Arch过敏免疫
更新日期:2020-07-01
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