MicroRNA-124 alleviates the lung injury in mice with septic shock through inhibiting the activation of the MAPK signaling pathway by downregulating MAPK14
MicroRNA-124 alleviates the lung injury in mice with septic shock through inhibiting the activation of the MAPK signaling pathway by downregulating MAPK14
复制标题
DOI：
10.1016/j.intimp.2019.105835
复制
发表时间：
2019-11-01
影响因子：
5.6
通讯作者：
Li, Na
中科院分区：
文献类型：
--
作者：
Pan, Weiyun;Wei, Na;Li, Na
目的：急性肺损伤（ALI）是一种死亡率较高的严重肺部疾病。研究强调，对ALI的免疫反应与肺部多种微小核糖核酸（miRNAs）表达的显著变化有关。在我们的研究中，我们推测miR - 124通过靶向丝裂原活化蛋白激酶14（MAPK14）全面抑制MAPK信号通路的激活，从而调节ALI的严重程度。
方法：通过一系列实验建立ALI小鼠模型。评估ALI小鼠组织中MAPK14和miR - 124的表达，并测定ALI小鼠炎症细胞因子的表达。通过一系列实验评估MAPK信号通路中相关激酶以及促炎反应关键细胞因子的表达。采用免疫组织化学和TUNEL染色检测ALI小鼠肺组织细胞的增殖和凋亡情况。
结果：在ALI小鼠组织中，miR - 124表达较低，MAPK14表达较高。miR - 124的过表达或MAPK14的沉默通过下调炎症细胞因子的表达缓解了ALI的症状，这能够从本质上抑制MAPK信号通路中相关蛋白以及下游促炎反应因子的表达，促进肺组织细胞的增殖并抑制其凋亡。MAPK14的过表达逆转了miR - 124过表达所诱导的表型变化。
结论：这些结果表明，miR - 124可通过后续靶向MAPK14抑制MAPK信号通路的激活来缓解ALI的症状。此外，miR - 124可能作为一种有用的生物标志物来缓解脓毒症休克诱导的肺损伤的严重程度。
Objective: Acute lung injury (ALI) is a severe lung disease with high mortality rate. Research has highlighted that the immune response to ALI is associated with significant changes in the expression of several microRNAs (miRNAs) in the lungs. In our research, we speculated that miR-124 moderated the severity of ALI through comprehensive suppression of the mitogen-activated protein kinase (MAPK) signaling pathway activation by targeting MAPK14.Methods: A mouse model of ALI was established by array of experiments. The expression of MAPK14 and miR-124 was assessed in the tissues of ALI mice and the expression of inflammatory cytokines in ALI mice was determined. The expression of the related kinases in the MAPK signaling pathway and key cytokines in the pro-inflammatory response were assessed by a series of experiments. Immunohistochemistry and TUNEL staining were adopted to detect lung tissue cell proliferation and apoptosis in mice with ALI.Results: MiR-124 was poorly expressed and MAPK14 was highly expressed in tissues of ALI mice. Overexpression of miR-124 or silence of MAPK14 alleviated the symptoms of ALI by down-regulating inflammatory cytokines expression, which could intrinsically suppress the expression of associated proteins in the MAPK signaling pathway and the downstream pro-inflammatory response factors, promote proliferation and inhibit apoptosis of lung tissue cells. Overexpression of MAPK14 inverted the phenotypic changes induced by overexpressing miR-124.Conclusion: These results indicated that miR-124 could alleviate the symptoms of ALI by inhibiting the activation of MAPK signaling pathway via subsequent targeting of MAPK14. Additionally, miR-124 may serve as a useful biomarker to alleviate the severity of septic shock-induced lung injury.