Department of Ultrasonography, China-Japan Union Hospital of Jilin University, Changchun, Jilin, 130033, China.
Department of Vascular Surgery, China-Japan Union Hospital of Jilin University, Changchun, Jilin, 130033, China.
Biochem Biophys Res Commun. 2018 Jun 7;500(3):589-596. doi: 10.1016/j.bbrc.2018.04.109. Epub 2018 Apr 24.
Pneumonia is a lower respiratory disease caused by pathogens or other factors. This study aimed to explore the roles and mechanism of long noncoding RNA HAGLROS in lipopolysaccharides (LPS)-induced inflammatory injury in pneumonia. The HAGLROS expression in serum of patients with acute stage pneumonia was detected. To induce pulmonary injury, WI-38 human lung fibroblasts were stimulated with lipopolysaccharides (LPS). The HAGLROS expressions in LPS-treated WI-38 cells and the effects of HAGLROS knockdown on the viability, apoptosis, and autophagy of LPS-induced cells were detected. Moreover, the regulatory relationship between HAGLROS and miR-100 was explored as well as the functional targets of miR-100 were identified. Furthermore, the regulatory relationship between miR-100 and PI3K/AKT/NF-κB pathway was elucidated. LncRNA HAGLROS was higher expressed in serum of patients with acute stage pneumonia compared with that in serum of healthy control. LPS caused WI-38 cell injury and increased HAGLROS levels. Downregulation of HAGLROS alleviated LPS-induced cell injury via increasing cell viability, and inhibiting apoptosis and autophagy. Moreover, there was a negative correlation between HAGLROS and miR-100, and the effects of HAGLROS downregulation on LPS-induced apoptosis and autophagy in WI-38 cells were by regulation of miR-100. Furthermore, NFΚB3 was verified as a functional target of miR-100 and effects of miR-100 inhibition on LPS-induced WI-38 cell injury were alleviated by knockdown of NFΚB3. Besides, Knockdown of HAGLROS inhibited the activation of PI3K/AKT/NF-κB pathway. Our findings reveal that downregulation of HAGLROS may alleviate LPS-induced inflammatory injury in WI-38 cells via modulating miR-100/NF-κB axis. HAGLROS/miR-100/NF-κB axis may provide a new strategy for treating acute stage of pneumonia.
肺炎是一种由病原体或其他因素引起的下呼吸道疾病。本研究旨在探讨长链非编码 RNA HAGLROS 在脂多糖（LPS）诱导的肺炎炎症损伤中的作用和机制。检测了急性肺炎患者血清中 HAGLROS 的表达。为了诱导肺损伤，用脂多糖（LPS）刺激 WI-38 人肺成纤维细胞。检测 LPS 处理的 WI-38 细胞中 HAGLROS 的表达以及 HAGLROS 敲低对 LPS 诱导细胞活力、凋亡和自噬的影响。此外，还探讨了 HAGLROS 与 miR-100 的调控关系以及 miR-100 的功能靶点。进一步阐明了 miR-100 与 PI3K/AKT/NF-κB 通路的调控关系。与健康对照组相比，急性肺炎患者血清中 HAGLROS 表达水平升高。LPS 导致 WI-38 细胞损伤并增加 HAGLROS 水平。下调 HAGLROS 通过增加细胞活力、抑制细胞凋亡和自噬来减轻 LPS 诱导的细胞损伤。此外，HAGLROS 与 miR-100 呈负相关，下调 HAGLROS 对 LPS 诱导的 WI-38 细胞凋亡和自噬的作用是通过调节 miR-100 实现的。此外，NFΚB3 被验证为 miR-100 的功能靶点，NFΚB3 的敲低可减轻 miR-100 抑制对 LPS 诱导的 WI-38 细胞损伤的作用。此外，下调 HAGLROS 抑制了 PI3K/AKT/NF-κB 通路的激活。我们的研究结果表明，下调 HAGLROS 可能通过调节 miR-100/NF-κB 轴减轻 LPS 诱导的 WI-38 细胞炎症损伤。HAGLROS/miR-100/NF-κB 轴可能为治疗急性肺炎提供新策略。
