State Key Laboratory of Trauma, Burns and Combined Injury, Department of Traumatic Surgery, Institute of Surgery Research, Daping Hospital, Military Medical University, Chongqing, 400042, China.
Cell Biol Int. 2019 Oct;43(10):1174-1183. doi: 10.1002/cbin.11098. Epub 2019 Jul 16.
Regeneration of pulmonary epithelial cells plays an important role in the recovery of acute lung injury (ALI), which is defined by pulmonary epithelial cell death. However, the mechanism of the regenerative capacity of alveolar epithelial cells is unknown. Using a lung injury mouse model induced by hemorrhagic shock and lipopolysaccharide, a protein mass spectrometry-based high-throughput screening and linage tracing technology to mark alveolar epithelial type 2 cells (AEC2s), we analyzed the mechanism of alveolar epithelial cells proliferation. We demonstrated that the expression of Hippo-yes-associated protein 1 (YAP1) key proteins were highly consistent with the regularity of the proliferation of alveolar epithelial type 2 cells after ALI. Furthermore, the results showed that YAP1+ cells in lung tissue after ALI were mainly Sftpc lineage-labeled AEC2s. An in vitro proliferation assay of AEC2s demonstrated that AEC2 proliferation was significantly inhibited by both YAP1 small interfering RNA and Hippo inhibitor. These findings revealed that YAP functioned as a key regulator to promote AEC2s proliferation, with the Hippo signaling pathway playing a pivotal role in this process.
肺上皮细胞的再生在急性肺损伤 (ALI) 的恢复中起着重要作用，ALI 的定义是肺上皮细胞死亡。然而，肺泡上皮细胞再生能力的机制尚不清楚。我们使用由失血性休克和脂多糖诱导的肺损伤小鼠模型，采用基于蛋白质质谱的高通量筛选和谱系追踪技术来标记肺泡上皮细胞 2 型 (AEC2)，分析了肺泡上皮细胞增殖的机制。结果表明，Hippo-yes 相关蛋白 1 (YAP1) 关键蛋白的表达与 ALI 后肺泡上皮细胞 2 型增殖的规律高度一致。此外，结果表明，ALI 后肺组织中的 YAP1+细胞主要是 Sftpc 谱系标记的 AEC2。体外 AEC2 增殖实验表明，YAP1 小干扰 RNA 和 Hippo 抑制剂均显著抑制 AEC2 增殖。这些发现表明 YAP 作为一种关键调节因子促进 AEC2 增殖，Hippo 信号通路在这个过程中起着关键作用。
