BML-111 通过调节 lncRNA MALAT1 的表达缓解急性肺损伤。
BML-111 alleviates acute lung injury through regulating the expression of lncRNA MALAT1.
机构信息
Department of Critical Care Medicine, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, Henan, China.
Department of Critical Care Medicine, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, Henan, China.
出版信息
Arch Biochem Biophys. 2018 Jul 1;649:15-21. doi: 10.1016/j.abb.2018.04.016. Epub 2018 Apr 25.
BML-111 is a lipoxin receptor agonist that plays a vital role on inflammation. MALAT1 is reported to mediate lung injury. ALI rat model was established using the method of venous cannula. Pulmonary microvascular endothelial cells (PMVEC) of rats were isolated using immunomagnetic separation method. Hematoxylin-eosin (HE) staining was performed to observe the lung injury degree. Real-time PCR and western blot were performed to detect the genes expression. ELIAS was used to determine the level of TNF-α and IL-6. RNA pull-down and RIP were carried out to affirm the relationship between MALAT1 and TLR4. The lung injury score and lung wet/dry weight ratio was significantly increased in ALI rats, while BML-111 treatment significantly decreased it, the HE staining directly revealed the lung injury. The expression of MALAT1 was decreased, while TLR4 was increased in ALI rats, BML-111 stimulation significantly reversed it. MALAT1 targets TLR4 to regulate its expression. TLR4 regulated the inflammation and cell apoptosis of PMVEC via NF-κB and p38 MAPK signaling pathway. The down-regulated MALAT1 mediates the mechanism of ALI by regulating of NF-κB and p38 MAPK signaling pathways via TLR4, while BML-111 stimulation significantly alleviated the ALI by regulating the expression of MALAT1.
BML-111 是一种脂氧素受体激动剂，在炎症中发挥着重要作用。MALAT1 被报道介导肺损伤。采用静脉插管法建立 ALI 大鼠模型。采用免疫磁珠分离法分离大鼠肺微血管内皮细胞（PMVEC）。进行苏木精-伊红（HE）染色观察肺损伤程度。实时 PCR 和 Western blot 检测基因表达。ELIAS 测定 TNF-α和 IL-6 水平。RNA 下拉和 RIP 用于证实 MALAT1 和 TLR4 之间的关系。在 ALI 大鼠中，肺损伤评分和肺湿/干重比显著增加，而 BML-111 治疗显著降低了它们，HE 染色直接揭示了肺损伤。在 ALI 大鼠中，MALAT1 的表达减少，而 TLR4 增加，BML-111 刺激显著逆转了这一现象。MALAT1 通过靶向 TLR4 调节其表达。TLR4 通过 NF-κB 和 p38 MAPK 信号通路调节 PMVEC 的炎症和细胞凋亡。下调的 MALAT1 通过 TLR4 调节 NF-κB 和 p38 MAPK 信号通路介导 ALI 的机制，而 BML-111 刺激通过调节 MALAT1 的表达显著缓解 ALI。
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