Department of Critical Care Medicine, Ren Ji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Department of Critical Care Medicine, Ren Ji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
BMJ Open Respir Res. 2023 Aug;10(1). doi: 10.1136/bmjresp-2023-001753.
Recent research has revealed that mechanical ventilation (MV) could initiate ventilator-induced lung injury along with the initiation of the process of pulmonary fibrosis (PF), leading to MV-induced PF (MVPF). However, the underlying mechanism remains unclear. This study aimed to explore the role of MV-induced extracellular vesicles (MV-EVs) and the c-Jun N-terminal kinase (JNK) signalling pathway in the pathogenesis of MVPF in vivo and in vitro. The process of MV is accompanied by the secretion of MV-EVs, which could induce lung fibroblast activation. Furthermore, single-cell RNA-sequencing analysis revealed that the JNK pathway in lung fibroblasts was activated after MV initiation. Inhibiting the JNK pathway could both restrain MV-EV-induced lung fibroblast activation in vitro or reduce the severity of MVPF in vivo. In conclusion, this study demonstrated that MV-EVs contribute to MVPF progression by activating lung fibroblasts via the JNK signalling pathway and that inhibiting the secretion of EV and the activation of the JNK signalling pathway is a promising strategy for treating MVPF.
最近的研究表明，机械通气（MV）会引发呼吸机诱导性肺损伤，同时引发肺纤维化（PF）过程，导致 MV 诱导的 PF（MVPF）。然而，其潜在机制尚不清楚。本研究旨在探讨 MV 诱导的细胞外囊泡（MV-EVs）和 c-Jun N-末端激酶（JNK）信号通路在体内和体外 MVPF 发病机制中的作用。MV 过程伴随着 MV-EVs 的分泌，这可能会诱导肺成纤维细胞的激活。此外，单细胞 RNA 测序分析显示，MV 启动后肺成纤维细胞中的 JNK 途径被激活。抑制 JNK 途径既能抑制 MV-EV 诱导的体外肺成纤维细胞激活，也能减轻体内 MVPF 的严重程度。总之，本研究表明，MV-EVs 通过激活 JNK 信号通路促进肺成纤维细胞激活，从而导致 MVPF 进展，抑制 EV 的分泌和 JNK 信号通路的激活是治疗 MVPF 的一种有前途的策略。
