Institute of Physical Science and Information Technology, Anhui University, Hefei 230601, China; Academy of Military Medical Sciences, Beijing 100850, China.
Department of Respiratory and Critical Care Diseases, 307 Hospital of PLA, Beijing 100071, China.
Int Immunopharmacol. 2019 Jun;71:68-75. doi: 10.1016/j.intimp.2019.03.017. Epub 2019 Mar 14.
Acute lung injury (ALI), a persistent lung inflammatory response syndrome, may evolve into acute respiratory distress syndrome (ARDS). Characterized by rapid onset, critical features, and a complex etiology, ALI remains a challenging critical respiratory disease. Recently, mesenchymal stem cells (MSCs) have provided a new solution for the treatment of ALI. We built a lipopolysaccharide (LPS)-induced ALI model in mice. After treatment with human umbilical cord mesenchymal stem cells (hUC-MSCs), FTY720, or a combination of hUC-MSCs and FTY207, the lung inflammatory response was apparently attenuated. To understand the mechanism underlying MSCs treatment of ALI at the genetic level, significant differentially expressed long non-coding RNAs (lncRNAs) between the treatment and model groups were analyzed using microarray technology. Moreover, genetic gene prediction, gene ontology (GO) analysis, pathway analysis, and transcription factor (TF) prediction were carried out. The results showed that a total of 66 lncRNAs were differentially expressed in all three treatment groups, including 8 up-regulated and 58 down-regulated lncRNAs. LncRNA A_30_P01029806 and A_30_P01029194, which were down-regulated, were involved in the signaling pathways closely related to ALI. Through further TF analysis, we identified several significant TFs which lay a foundation for revealing the mechanism underlying lncRNAs treatment of ALI. LncRNA A_30_P01029806 and A_30_P01029194 may serve as candidate biomarkers in the diagnosis and treatment of ALI.
急性肺损伤（ALI）是一种持续的肺部炎症反应综合征，可能发展为急性呼吸窘迫综合征（ARDS）。ALI 以发病迅速、关键特征和复杂病因为特征，仍然是一种具有挑战性的严重呼吸系统疾病。最近，间充质干细胞（MSCs）为 ALI 的治疗提供了新的解决方案。我们构建了脂多糖（LPS）诱导的 ALI 小鼠模型。在用人脐带间充质干细胞（hUC-MSCs）、FTY720 或 hUC-MSCs 和 FTY207 联合治疗后，肺部炎症反应明显减弱。为了在遗传水平上了解 MSCs 治疗 ALI 的机制，我们使用微阵列技术分析了治疗组和模型组之间显著差异表达的长非编码 RNA（lncRNA）。此外，还进行了遗传基因预测、基因本体论（GO）分析、通路分析和转录因子（TF）预测。结果表明，在所有三种治疗组中，共有 66 个 lncRNA 差异表达，包括 8 个上调和 58 个下调 lncRNA。下调的 lncRNA A_30_P01029806 和 A_30_P01029194 参与了与 ALI 密切相关的信号通路。通过进一步的 TF 分析，我们确定了几个重要的 TF，为揭示 lncRNA 治疗 ALI 的机制奠定了基础。lncRNA A_30_P01029806 和 A_30_P01029194 可能作为 ALI 诊断和治疗的候选生物标志物。
