Department of ICU, The First Hospital of Jilin University, Changchun 130021, PR China.
Department of the First Operating Room, The First Hospital of Jilin University, Changchun 130021, PR China.
Int Immunopharmacol. 2019 Nov;76:105835. doi: 10.1016/j.intimp.2019.105835. Epub 2019 Aug 30.
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.
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.
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.
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.
急性肺损伤（ALI）是一种死亡率很高的严重肺部疾病。研究表明，ALI 的免疫反应与肺部几种 microRNAs（miRNAs）的表达显著变化有关。在我们的研究中，我们推测 miR-124 通过靶向 MAPK14 全面抑制丝裂原活化蛋白激酶（MAPK）信号通路的激活，从而调节 ALI 的严重程度。
通过一系列实验建立了 ALI 小鼠模型。评估了 ALI 小鼠组织中 MAPK14 和 miR-124 的表达，以及 ALI 小鼠中炎症细胞因子的表达。通过一系列实验评估了 MAPK 信号通路中相关激酶和促炎反应中的关键细胞因子的表达。采用免疫组织化学和 TUNEL 染色法检测 ALI 小鼠肺组织细胞的增殖和凋亡。
miR-124 在 ALI 小鼠组织中表达水平较低，MAPK14 表达水平较高。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，这可以内在抑制 MAPK 信号通路和下游促炎反应因子相关蛋白的表达，促进肺组织细胞的增殖并抑制其凋亡。MAPK14 的过表达反转了过表达 miR-124 诱导的表型变化。
这些结果表明，miR-124 可以通过随后靶向 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，用于减轻脓毒症诱导的肺损伤的严重程度。
