Liang Wei-Jun, Zeng Xiao-Yuan, Jiang Sha-Li, Tan Hong-Yi, Yan Mu-Yun, Yang Hong-Zhong
Department of Respiratory Medicine, Changsha Central Hospital, Changsha, P.R. China.
Department of Pathology, Changsha Central Hospital, Changsha, P.R. China.
Cell Biol Int. 2020 Jan;44(1):317-326. doi: 10.1002/cbin.11235. Epub 2019 Sep 9.
Acute lung injury (ALI) caused by sepsis occurs early and the condition is severe, and is also an important reason for accelerating the death of patients. Increasing evidence has identified long non-coding RNA (lncRNA) metastasis associated in lung adenocarcinoma transcript 1 (MALAT1) as a regulator of ALI. However, the potential mechanism underlying MALAT1 on ALI still needs further identification. To explore the mechanisms of gene regulation expression mediated by MALAT1 through miR-149/MyD88 in lung injury inflammation, we constructed a lung injury inflammatory model using the lipopolysaccharides (LPS)-induced method and quantificated the cytokines and signaling cascade molecules as well as miR-149. The MALAT1, myeloid differentiation factor 88 (MyD88), tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and IL-6 levels were significantly increased, and the nuclear factor-κB (NF-κB) pathway was activated, but the miR-149 level was decreased in the LPS-induced ALI model. miR-149 directly targeted both lncRNA MALAT1 and the MyD88 gene. Knockdown of MALAT1 down-regulated the levels of MyD88, TNF-α, IL-1β, and IL-6, and inhibited the NF-κB pathway. However, MALAT1 knockdown up-regulated the expression of miR-149. Overexpression of miR-149 down-regulated MyD88, TNF-α, IL-1β, and IL-6 levels, and inhibited the NF-κB pathway. MALAT1 acts as a pro-inflammatory factor in ALI via the miR-149/MyD88/NF-κB axis and is therefore a potential novel therapeutic target for ALI treatment.
脓毒症引起的急性肺损伤（ALI）发病早且病情严重，也是加速患者死亡的重要原因。越来越多的证据表明，长链非编码RNA（lncRNA）肺腺癌转移相关转录本1（MALAT1）是ALI的一个调节因子。然而，MALAT1对ALI作用的潜在机制仍需进一步明确。为了探究MALAT1通过miR-149/髓样分化因子88（MyD88）介导的基因调控表达在肺损伤炎症中的机制，我们采用脂多糖（LPS）诱导法构建了肺损伤炎症模型，并对细胞因子、信号级联分子以及miR-149进行了定量分析。在LPS诱导的ALI模型中，MALAT1、MyD88、肿瘤坏死因子-α（TNF-α）、白细胞介素-1β（IL-1β）和IL-6水平显著升高，核因子-κB（NF-κB）通路被激活，但miR-149水平降低。miR-149直接靶向lncRNA MALAT1和MyD88基因。敲低MALAT1可下调MyD88、TNF-α、IL-1β和IL-6的水平，并抑制NF-κB通路。然而，敲低MALAT1可上调miR-149的表达。过表达miR-149可下调MyD88、TNF-α、IL-1β和IL-6的水平，并抑制NF-κB通路。MALAT1通过miR-149/MyD88/NF-κB轴在ALI中作为促炎因子发挥作用，因此是ALI治疗潜在的新型治疗靶点。
