miR-142-5p 和 miR-130a-3p 调节肺巨噬细胞极化和哮喘气道重塑。,Immunology and Cell Biology

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miR-142-5p 和 miR-130a-3p 调节肺巨噬细胞极化和哮喘气道重塑。
Immunology and Cell Biology ( IF 3.2 ) Pub Date : 2020-06-10 , DOI: 10.1111/imcb.12369
Jianting Shi ₁ , Ming Chen ₁ , Lihua Ouyang ₂ , Qiujie Wang ₁ , Yimin Guo ₁ , Linjie Huang ₁ , Shanping Jiang ₁

Affiliation

巨噬细胞是哮喘发展和进展的关键调节剂，促进受影响患者的有害气道重塑。免疫细胞功能受到 microRNA (miRNA) 的严格调控，但这些 miRNA 如何影响哮喘背景下巨噬细胞介导的气道重塑仍有待确定。在这项研究中，我们利用基于卵清蛋白 (OVA) 的哮喘小鼠模型来评估 miRNA 在这些巨噬细胞中的重要性。我们发现，来自 OVA 致敏和暴露于 OVA 的小鼠的巨噬细胞表达了更高水平的 M2 样表型标志物，并表现出 miR-142-5p 和 miR-130a-3p 的显着改变。当这些分离的肺巨噬细胞在体外培养时, 我们确定用 miR-142-5p 反义寡核苷酸 (ASO) 或 miR-130a-3p 模拟物转染它们足以抑制白细胞介素-4 诱导 M2 细胞因子产生的能力。我们还证实了这些 miRNA 在模拟哮喘的Ccr2 ^-/-鼠模型系统中的体内相关性。具体来说，我们确定用 miR-142-5p ASO 和/或 miR-130a-3p 模拟物转染单核细胞足以破坏这些细胞促进气道重塑的能力。因此，这些发现表明 miR-142-5p 和 miR-130a-3p 失调是控制巨噬细胞极化和 OVA 致敏小鼠相关气道重塑的重要因素。

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miR-142-5p and miR-130a-3p regulate pulmonary macrophage polarization and asthma airway remodeling.

Macrophages are key regulators of the development and progression of asthma, facilitating deleterious airway remodeling in affected patients. Immune cell function is tightly regulated by microRNAs (miRNAs), but how these miRNAs impact macrophage‐mediated airway remodeling in the context of asthma remains to be determined. In this study, we utilized an ovalbumin (OVA)‐based murine model of asthma to evaluate the importance of miRNAs within these macrophages. We found that macrophages from mice that had been sensitized with and exposed to OVA expressed higher levels of M2‐like phenotypic markers and exhibited significantly altered expression of both miR‐142‐5p and miR‐130a‐3p. When these isolated pulmonary macrophages were cultured in vitro, we determined that transfecting them with miR‐142‐5p antisense oligonucleotide (ASO) or miR‐130a‐3p mimics was sufficient to inhibit the ability of interleukin‐4 to induce M2 cytokine production. We additionally confirmed the in vivo relevance of these miRNAs in a Ccr2^−/− murine model system mimicking asthma. Specifically, we determined that transfecting monocytes with miR‐142‐5p ASO and/or miR‐130a‐3p mimics was sufficient to disrupt the ability of these cells to promote airway remodeling. As such, these findings reveal that miR‐142‐5p and miR‐130a‐3p dysregulation are important factors governing the polarization of macrophages and associated airway remodeling in OVA‐sensitized mice.

更新日期：2020-06-10

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