Department of Pulmonary and Critical Care Medicine, The First People's Hospital of Yunnan Province, Kunming, China.
J Cell Mol Med. 2021 Mar;25(5):2725-2729. doi: 10.1111/jcmm.15844. Epub 2021 Feb 1.
The over-activation of inflammation is involved in the pathogenesis of smoke-induced lung injury (SILI), while Rb3 treatment may alleviate smoke-induced lung injury by down-regulating the expression of H19, a regulator of miR-29b expression. Moreover, HMGB1 is an important mediator of inflammation. Therefore, in this study, we set up an animal model of SILI and treated it with Rb3 to study the effect of Rb3 on the treatment of SILI and the involvement of H19/miR-29b/HMGB1/TLR4 signalling. SILI mice treated with Rb3 before H&E staining and TUNEL assay were conducted to observe the pathological damages and status of apoptosis in each group. Real-time PCR, Western blot, computational analysis and luciferase assays were utilized to establish the signalling pathway involved in the pathogenesis of SILI and the action of Rb3 treatment. Rb3 treatment alleviated pathological changes in the lungs while decreasing the levels of W/D ratio and cell apoptotic index. H19 was validated to sponge miR-29b-3p, while HMGB1 mRNA was validated to be a target gene of miR-29b-3. As a result, a signalling pathway of H19/miR-29b-3p/HMGB1 was established. Cell viability was evidently reduced after 72 hours of treatment with CSE, but the treatment of Rb3 elevated the expression of H19 and HMBG1 in the presence of CSE. Also, CSE-induced inhibition of miR-29b-3p expression was restored by Rb3. The findings of this study collectively demonstrated that Rb3 exhibited its therapeutic effect during the treatment of SILI via modulating the H19/miR-29b-3p/HMBG1 signalling pathway.
炎症的过度激活参与了吸烟诱导的肺损伤（SILI）的发病机制，而 Rb3 治疗可能通过下调 H19 的表达来减轻吸烟引起的肺损伤，H19 是 miR-29b 表达的调节因子。此外，HMGB1 是炎症的重要介质。因此，在本研究中，我们建立了 SILI 动物模型，并使用 Rb3 进行治疗，以研究 Rb3 对 SILI 治疗的影响以及 H19/miR-29b/HMGB1/TLR4 信号通路的参与。在用 H&E 染色和 TUNEL 检测进行 SILI 小鼠治疗之前，观察了每组的病理损伤和细胞凋亡状态。实时 PCR、Western blot、计算分析和荧光素酶测定用于建立 SILI 发病机制和 Rb3 治疗作用涉及的信号通路。Rb3 治疗减轻了肺部的病理变化，同时降低了 W/D 比值和细胞凋亡指数。验证 H19 可吸附 miR-29b-3p，而 HMGB1 mRNA 验证为 miR-29b-3p 的靶基因。因此，建立了 H19/miR-29b-3p/HMGB1 信号通路。CSE 处理 72 小时后，细胞活力明显降低，但 Rb3 治疗在 CSE 存在的情况下上调了 H19 和 HMBG1 的表达。此外，Rb3 恢复了 CSE 诱导的 miR-29b-3p 表达抑制。这项研究的结果表明，Rb3 通过调节 H19/miR-29b-3p/HMBG1 信号通路在 SILI 治疗中发挥了治疗作用。
