Proliferation and transdifferentiation of lung stem cells (LSCs) could promote lung injury repair. The distal airways of the lung are innervated by the vagus nerve. Vagal-alpha7 nicotinic acetylcholine receptor (α7nAChR) signaling plays a key role in regulating lung infection and inflammation; however, whether this pathway could regulate LSCs remains unknown. LSCs (Sca1+CD45−CD31− cells) were isolated and characterized according to a previously published protocol. α7nAChR knockout mice and wild-type littermates were intratracheally challenged with lipopolysaccharide (LPS) to induce lung injury. A cervical vagotomy was performed to study the regulatory effect of the vagus nerve on LSCs-mediated lung repair. α7nAChR agonist or fibroblast growth factor 10 (FGF10) was intratracheally delivered to mice. A single-cell suspension of lung cells was analyzed by flow cytometry. Lung tissues were collected for histology, quantitative real-time polymerase chain reaction (RT-PCR), and immunohistochemistry. We found that LSCs maintained multilineage differentiation ability and transdifferentiated into alveolar epithelial type II cells (AEC2) following FGF10 stimulation in vitro. Vagotomy or α7nAChR deficiency reduced lung Ki67+ LSCs expansion and hampered the resolution of LPS-induced lung injury. Vagotomy or α7nAChR deficiency decreased lung FGF10 expression and the number of AEC2. The α7nAChR agonist-GTS-21 reversed the reduction of FGF10 expression in the lungs, as well as the number of Ki67+ cells, LSCs, Ki67+ LSCs, and AEC2 in LPS-challenged vagotomized mice. Supplementation with FGF10 counteracted the loss of Ki67+ LSCs and AEC2 in LPS-challenged α7nAChR knockout mice. The vagus nerve deploys α7nAChR to enhance LSCs proliferation and transdifferentiation and promote lung repair in an FGF10-dependent manner during LPS-induced lung injury.

中文翻译：

---

Vagal-α7nAChR 信号在肺损伤修复过程中通过成纤维细胞生长因子 10 促进肺干细胞再生。

肺干细胞（LSCs）的增殖和转分化可以促进肺损伤修复。肺的远端气道由迷走神经支配。迷走神经-α7 烟碱型乙酰胆碱受体 (α7nAChR) 信号传导在调节肺部感染和炎症中起关键作用；然而，该途径是否可以调节 LSCs 仍然未知。LSC（Sca1+CD45-CD31-细胞）根据先前公布的方案进行分离和表征。用脂多糖 (LPS) 对 α7nAChR 敲除小鼠和野生型同窝仔鼠进行气管内攻击以诱导肺损伤。进行颈迷走神经切断术以研究迷走神经对 LSCs 介导的肺修复的调节作用。将 α7nAChR 激动剂或成纤维细胞生长因子 10 (FGF10) 经气管内递送至小鼠。通过流式细胞术分析肺细胞的单细胞悬液。收集肺组织用于组织学、定量实时聚合酶链反应 (RT-PCR) 和免疫组织化学。我们发现 LSC 在体外 FGF10 刺激后保持多向分化能力并转分化为肺泡上皮 II 型细胞 (AEC2)。迷走神经切断术或 α7nAChR 缺乏会降低肺 Ki67+ LSCs 的扩张并阻碍 LPS 诱导的肺损伤的消退。迷走神经切断术或 α7nAChR 缺乏会降低肺 FGF10 表达和 AEC2 的数量。α7nAChR 激动剂-GTS-21 逆转了 LPS 挑战迷走神经切断小鼠肺中 FGF10 表达的减少，以及 Ki67+ 细胞、LSC、Ki67+ LSC 和 AEC2 的数量。补充 FGF10 可抵消 LPS 攻击的 α7nAChR 敲除小鼠中 Ki67+ LSC 和 AEC2 的损失。在 LPS 诱导的肺损伤期间，迷走神经部署 α7nAChR 以增强 LSCs 增殖和转分化，并以 FGF10 依赖性方式促进肺修复。