Li Congcong, Liu Manling, Bo Liyan, Liu Wei, Liu Qingqing, Chen Xiangjun, Xu Dunquan, Li Zhichao, Jin Faguang
Department of Respiration, Tangdu Hospital, Fourth Military Medical University, Xi'an, Shaanxi 710038, P.R. China.
Department of Pathology and Pathophysiology, Fourth Military Medical University, Xi'an, Shaanxi 710032, P.R. China.
Mol Med Rep. 2016 Dec;14(6):5033-5040. doi: 10.3892/mmr.2016.5860. Epub 2016 Oct 19.
Nuclear factor of activated T cells 5 (NFAT5) is a transcription factor that can be activated by extracellular tonicity. It has been reported that NFAT5 may increase the transcription of certain osmoprotective genes in the renal system, and the aim of the current study was to explore the role of NFAT5 in seawater inhalation‑induced acute lung injury. Though establishing the model of seawater inhalation‑induced acute lung injury, it was demonstrated that seawater inhalation enhanced the transcription and protein expression of NFAT5 (evaluated by reverse transcription‑polymerase chain reaction, immunohistochemistry stain and western blotting) and activation of nuclear factor (NF)‑κB (evaluated by western blotting and mRNA expression levels of three NF‑κB‑dependent genes) both in lung tissue and rat alveolar macrophage cells (NR8383 cells). When expression of NFAT5 was reduced in NR8383 cells using an siRNA targeted to NFAT5, the phosphorylation of NF‑κB and transcription of NF‑κB‑dependent genes were significantly reduced. In addition, the elevated content of certain inflammatory cytokines [tumor necrosis factor α, interleukin (IL)‑1 and IL‑8] were markedly reduced. In conclusion, NFAT5 serves an important pathophysiological role in seawater inhalation‑induced acute lung injury by modulating NF‑κB activity, and these data suggest that NFAT5 may be a promising therapeutic target.
活化T细胞核因子5（NFAT5）是一种可被细胞外张力激活的转录因子。据报道，NFAT5可能会增加肾系统中某些渗透压保护基因的转录，而本研究的目的是探讨NFAT5在海水吸入诱导的急性肺损伤中的作用。通过建立海水吸入诱导的急性肺损伤模型，结果表明，海水吸入增强了肺组织和大鼠肺泡巨噬细胞（NR8383细胞）中NFAT5的转录和蛋白表达（通过逆转录-聚合酶链反应、免疫组织化学染色和蛋白质印迹法评估）以及核因子（NF）-κB的激活（通过蛋白质印迹法和三个NF-κB依赖性基因的mRNA表达水平评估）。当使用靶向NFAT5的小干扰RNA（siRNA）降低NR8383细胞中NFAT5的表达时，NF-κB的磷酸化和NF-κB依赖性基因的转录显著降低。此外，某些炎性细胞因子[肿瘤坏死因子α、白细胞介素（IL）-1和IL-8]含量的升高也明显降低。总之，NFAT5通过调节NF-κB活性在海水吸入诱导的急性肺损伤中发挥重要的病理生理作用，这些数据表明NFAT5可能是一个有前景的治疗靶点。
