Lung injury in axolotl salamanders induces an organ-wide proliferation response

Background Ambystoma mexicanum, the axolotl salamander, is a classic model organism used to study vertebrate regeneration. It is assumed that axolotls regenerate most tissues, but the exploration of lung regeneration has not been performed until now. Results Unlike the blastema-based response used during appendage regeneration, lung amputation led to organ-wide proliferation. Pneumocytes and mesenchymal cells responded to injury by increased proliferation throughout the injured lung, which led to a recovery in lung mass and morphology by 56 days post-amputation. Receptors associated with the Neuregulin signaling pathway were upregulated at one and 3 weeks post lung amputation. We show expression of the ligand, neuregulin, in the I/X cranial nerve that innervates the lung and cells within the lung. Supplemental administration of Neuregulin peptide induced widespread proliferation in the lung similar to an injury response, suggesting that neuregulin signaling may play a significant role during lung regeneration. Conclusion Our study characterizes axolotl lung regeneration. We show that the lung responds to injury by an organ-wide proliferative response of multiple cell types, including pneumocytes, to recover lung mass.

Automated summary

The study characterizes the process of lung regeneration in axolotls, showing that the lung responds to injury with a widespread proliferative response of multiple cell types, including pneumocytes, to recover lung mass. Receptors associated with the Neuregulin signaling pathway were upregulated post lung amputation, and supplemental administration of Neuregulin peptide induced proliferation in the lung, indicating a potential significant role in lung regeneration.