Effects of bone marrow-derived mesenchymal stromal cells on gene expression in human alveolar type II cells exposed to TNF-α, IL-1β, and IFN-γ.
Effects of bone marrow-derived mesenchymal stromal cells on gene expression in human alveolar type II cells exposed to TNF-α, IL-1β, and IFN-γ.
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DOI：
10.14814/phy2.13831
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发表时间：
2018-08
影响因子：
2.5
通讯作者：
Matthay MA
中科院分区：
文献类型：
--
作者：
Schwede M;Wilfong EM;Zemans RL;Lee PJ;Dos Santos C;Fang X;Matthay MA
急性呼吸窘迫综合征（ARDS）常见于危重患者，死亡率较高。间充质基质细胞 (MSC) 在 ARDS 动物模型中表现出治疗潜力，其益处部分是通过与 II 型肺泡 (ATII) 细胞的相互作用实现的。然而，MSC 对人类 ATII 细胞的影响尚未得到充分研究。利用之前发表的微阵列数据，我们对人类 ATII 细胞进行了全基因组差异基因表达分析，这些细胞 (1) 未受刺激，(2) 暴露于促炎细胞因子 (CytoMix)，或 (3) 暴露于促炎细胞因子加 MSC。结果通过 qPCR 得到验证。当暴露于促炎细胞因子或促炎细胞因子加 MSC 时，肺泡 II 型细胞差异表达数百个基因。促炎细胞因子的刺激增加了炎症基因的表达，并下调了与表面活性剂功能和肺泡液清除相关的基因。其中一些变化，包括一些细胞因子和与表面活性剂相关的基因的表达，通过暴露于间充质干细胞而被逆转。此外，间充质干细胞诱导其他潜在有益基因的上调，例如与细胞外基质重塑相关的基因。我们通过 qPCR 证实了其中一些基因表达变化。因此，当暴露于炎性细胞因子时，ATII细胞下调与表面活性剂和肺泡液清除相关的基因，并且间充质基质细胞部分逆转许多这些基因表达变化。
The acute respiratory distress syndrome (ARDS) is common in critically ill patients and has a high mortality rate. Mesenchymal stromal cells (MSCs) have demonstrated therapeutic potential in animal models of ARDS, and their benefits occur in part through interactions with alveolar type II (ATII) cells. However, the effects that MSCs have on human ATII cells have not been well studied. Using previously published microarray data, we performed genome‐wide differential gene expression analyses of human ATII cells that were (1) unstimulated, (2) exposed to proinflammatory cytokines (CytoMix), or (3) exposed to proinflammatory cytokines plus MSCs. Findings were validated by qPCR. Alveolar type II cells differentially expressed hundreds of genes when exposed either to proinflammatory cytokines or to proinflammatory cytokines plus MSCs. Stimulation with proinflammatory cytokines increased expression of inflammatory genes and downregulated genes related to surfactant function and alveolar fluid clearance. Some of these changes, including expression of some cytokines and genes related to surfactant, were reversed by exposure to MSCs. In addition, MSCs induced upregulation of other potentially beneficial genes, such as those related to extracellular matrix remodeling. We confirmed several of these gene expression changes by qPCR. Thus, ATII cells downregulate genes associated with surfactant and alveolar fluid clearance when exposed to inflammatory cytokines, and mesenchymal stromal cells partially reverse many of these gene expression changes.