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微小RNA-7缺乏通过上调KLF4改善急性肺损伤的病理状况。

MicroRNA-7 Deficiency Ameliorates the Pathologies of Acute Lung Injury through Elevating KLF4.

作者信息

Zhao Juanjuan, Chen Chao, Guo Mengmeng, Tao Yijin, Cui PanPan, Zhou Ya, Qin Nalin, Zheng Jing, Zhang Jidong, Xu Lin

机构信息

Department of Immunology, Zunyi Medical College , Guizhou , China.

Department of Medical Physics, Zunyi Medical College , Guizhou , China.

出版信息

Front Immunol. 2016 Oct 7;7:389. doi: 10.3389/fimmu.2016.00389. eCollection 2016.

Abstract

Recent evidence showed that microRNA-7 (miR-7) played an important role in the pathologies of lung-related diseases. However, the potential role of miR-7 in acute lung injury (ALI) still remains poorly understood. Here, we assessed the effect of miR-7 deficiency on the pathology of ALI. We, first, found that the expression of miR-7 was upregulated in lung tissue in murine LPS-induced ALI model. Notably, we generated miR-7 knock down mice by using miRNA-Sponge technique and found that miR-7 deficiency could ameliorate the pathologies of lung as evidenced by accelerated body weight recovery, reduced level of bronchoalveolar lavage (BAL) proinflammatory cytokines and decreased number of BAL cells in ALI mice. Moreover, the proportion and number of various immune cells in BAL, including innate immune cell F4/80 macrophages, γδT cells, NK1.1 T cells, and CD11cDCs, as well as adaptive immune cell CD4 T cells and CD8 T cells, also significantly changed, respectively. Mechanistic evidence showed that KLF4, a target molecule of miR-7, was upregulated in lung tissues in ALI model, accompanied by altered transduction of NF-κB, AKT, and ERK pathway. These data provided a previously unknown role of miR-7 in pathology of ALI, which could ultimately aid the understanding of development of ALI and the development of new therapeutic strategies against clinical inflammatory lung diseases.

摘要

近期证据表明,微小RNA-7(miR-7)在肺部相关疾病的病理过程中发挥重要作用。然而,miR-7在急性肺损伤(ALI)中的潜在作用仍知之甚少。在此,我们评估了miR-7缺陷对ALI病理的影响。首先,我们发现在小鼠脂多糖诱导的ALI模型中,肺组织中miR-7的表达上调。值得注意的是,我们通过使用miRNA-Sponge技术构建了miR-7敲低小鼠,发现miR-7缺陷可改善肺部病理状况,这表现为ALI小鼠体重恢复加快、支气管肺泡灌洗(BAL)促炎细胞因子水平降低以及BAL细胞数量减少。此外,BAL中各种免疫细胞的比例和数量,包括固有免疫细胞F4/80巨噬细胞、γδT细胞、NK1.1 T细胞和CD11cDCs,以及适应性免疫细胞CD4 T细胞和CD8 T细胞,也分别发生了显著变化。机制研究证据表明,miR-7的靶分子KLF4在ALI模型的肺组织中上调,同时伴有NF-κB、AKT和ERK信号通路转导的改变。这些数据揭示了miR-7在ALI病理中此前未知的作用,这最终可能有助于理解ALI的发病机制以及开发针对临床炎症性肺病的新治疗策略。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7779/5054040/1dd003d2efb6/fimmu-07-00389-g001.jpg

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