Department of Intensive Care Unit, Tengzhou Central People's Hospital, Tengzhou, China.
Clin Exp Pharmacol Physiol. 2020 Aug;47(8):1448-1454. doi: 10.1111/1440-1681.13315. Epub 2020 Apr 22.
Micro RNA (miRNA) and mitogen-activated protein kinase (MAPK) are reported as the crucial regulators of inflammatory responses in acute lung injury (ALI). This study will explore the role of the miR-342/MAPK1 axis in regulation of lipopolysaccharide (LPS)-induced ALI. We found that miR-342 was down-regulated in LPS-induced A549 cells compared with the control group with DMSO, accompanied by elevated inflammatory cytokines and apoptosis. Over-expression of miR-342 reduced LPS-induced inflammatory responses and apoptosis in LPS-stimulated A549 cells, and had a protective role in LPS-treated mice with ALI by decreasing levels of inflammatory cytokines, improving survival of mice with ALI, and ameliorating the lung permeability. Dual-luciferase reporter gene assay demonstrated that miR-342 regulated the expression of MAPK1 by directly targeting its 3' untranslated region (3'-UTR). Mechanistically, MAPK1 silencing abrogated LPS-induced inflammatory injury in A549 cells, and partially enhanced the protective effect of miR-342. Therefore, miR-342 attenuates LPS-induced ALI by targeting MAPK1 expression, thereby protecting against A549 cell injury induced by LPS and lung injury of mice with ALI.
微 RNA（miRNA）和丝裂原活化蛋白激酶（MAPK）被报道为急性肺损伤（ALI）中炎症反应的关键调节因子。本研究将探讨 miR-342/MAPK1 轴在调节脂多糖（LPS）诱导的 ALI 中的作用。我们发现，与 DMSO 处理的对照组相比，LPS 诱导的 A549 细胞中 miR-342 下调，同时炎症细胞因子和细胞凋亡增加。miR-342 的过表达可减少 LPS 刺激的 A549 细胞中的炎症反应和细胞凋亡，并通过降低炎症细胞因子水平、提高 ALI 小鼠的存活率以及改善肺通透性，对 LPS 处理的 ALI 小鼠具有保护作用。双荧光素酶报告基因检测表明，miR-342 通过直接靶向 MAPK1 的 3'非翻译区（3'-UTR）来调节其表达。在机制上，沉默 MAPK1 可消除 LPS 诱导的 A549 细胞炎症损伤，并部分增强 miR-342 的保护作用。因此，miR-342 通过靶向 MAPK1 表达来减轻 LPS 诱导的 ALI，从而防止 LPS 诱导的 A549 细胞损伤和 ALI 小鼠的肺损伤。
