Department of Respiratory Medicine, Center of Medical Endoscopy, Affiliated Fuzhou First Hospital of Fujian Medical University, Fuzhou, Fujian, China.
J Biochem Mol Toxicol. 2022 Jul;36(7):e23060. doi: 10.1002/jbt.23060. Epub 2022 Mar 31.
In this study, we explored to detect the effects and mechanism of bone-marrow-derived mesenchymal stem cells (BMSCs) on ventilator-induced lung injury (VILI). We transplanted BMSCs in mice and then induced VILI using mechanical ventilation (MV) treatment. The pathological changes, the content of PaO and PaCO , wet/dry weight ratio (W/D) of the lung, levels of tumor necrosis factor-α and interleukin-6 in bronchoalveolar lavage fluid, and apoptosis were detected. The autophagy-associated factor p62, LC3, and Beclin-1 expression were analyzed by western blot. The quantitative polymerase chain reaction was applied to detect abnormally expressed microRNAs, including miR-155-5p. Subsequently, we overexpressed miR-155-5p in VILI mice to detect the effects of miR-155-5p on MV-induced lung injury. Then, we carried out bioinformatics analysis to verify the BMSCs-regulated miR-155-5p that target messenger RNA. It was observed that BMSCs transplantation mitigated the severity of VILI in mice. BMSCs transplantation reduced lung inflammation, strengthened the arterial oxygen partial pressure, and reduced apoptosis and the W/D of the lung. BMSCs promoted autophagy of pulmonary endothelial cells accompanied by decreased p62 and increased LC3 II/I and Beclin-1. BMSCs increased the levels of miR-155-5p in VILI mice. Overexpression of miR-155-5p alleviated lung injury in VILI mice following reduced apoptosis and increased autophagy. Finally, TAB2 was identified as a downstream target of miR-155-5p and regulated by miR-155-5p. BMSCs may protect lung tissues from MV-induced injury, inhibit lung inflammation, promote autophagy through upregulating of miR-155-5p.
在这项研究中，我们探讨了骨髓间充质干细胞（BMSCs）对呼吸机诱导肺损伤（VILI）的作用和机制。我们将 BMSCs 移植到小鼠体内，然后使用机械通气（MV）治疗诱导 VILI。检测肺部病理变化、PaO 和 PaCO 含量、肺湿/干重比（W/D）、支气管肺泡灌洗液中肿瘤坏死因子-α和白细胞介素-6水平以及细胞凋亡情况。采用 Western blot 分析自噬相关因子 p62、LC3 和 Beclin-1 的表达。应用定量聚合酶链反应检测异常表达的 microRNAs，包括 miR-155-5p。随后，我们在 VILI 小鼠中过表达 miR-155-5p，以检测 miR-155-5p 对 MV 诱导的肺损伤的影响。然后，我们进行了生物信息学分析，以验证 BMSCs 调节的 miR-155-5p 靶向信使 RNA。结果观察到，BMSCs 移植减轻了小鼠 VILI 的严重程度。BMSCs 移植减少了肺炎症，增强了动脉血氧分压，减少了细胞凋亡和肺 W/D。BMSCs 促进了肺内皮细胞的自噬，同时降低了 p62，增加了 LC3 II/I 和 Beclin-1。BMSCs 增加了 VILI 小鼠中 miR-155-5p 的水平。过表达 miR-155-5p 可减轻 VILI 小鼠的肺损伤，减少细胞凋亡，增加自噬。最后，鉴定出 TAB2 是 miR-155-5p 的下游靶标，并受 miR-155-5p 调节。BMSCs 可能通过上调 miR-155-5p 来保护肺组织免受 MV 诱导的损伤，抑制肺炎症，促进自噬。
