| First Author | Chen X | Year | 2020 |
| Journal | Stem Cell Res Ther | Volume | 11 |
| Issue | 1 | Pages | 230 |
| PubMed ID | 32522255 | Mgi Jnum | J:310484 |
| Mgi Id | MGI:6762758 | Doi | 10.1186/s13287-020-01757-w |
| Citation | Chen X, et al. (2020) Vagal-alpha7nAChR signaling promotes lung stem cells regeneration via fibroblast growth factor 10 during lung injury repair. Stem Cell Res Ther 11(1):230 |
| abstractText | BACKGROUND: 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 (alpha7nAChR) signaling plays a key role in regulating lung infection and inflammation; however, whether this pathway could regulate LSCs remains unknown. METHODS: LSCs (Sca1(+)CD45(-)CD31(-) cells) were isolated and characterized according to a previously published protocol. alpha7nAChR 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. alpha7nAChR 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. RESULTS: We found that LSCs maintained multilineage differentiation ability and transdifferentiated into alveolar epithelial type II cells (AEC2) following FGF10 stimulation in vitro. Vagotomy or alpha7nAChR deficiency reduced lung Ki67(+) LSCs expansion and hampered the resolution of LPS-induced lung injury. Vagotomy or alpha7nAChR deficiency decreased lung FGF10 expression and the number of AEC2. The alpha7nAChR 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 alpha7nAChR knockout mice. CONCLUSIONS: The vagus nerve deploys alpha7nAChR to enhance LSCs proliferation and transdifferentiation and promote lung repair in an FGF10-dependent manner during LPS-induced lung injury. |
