Neuregulin-1 exerts molecular control over axolotl lung regeneration through ErbB family receptors

ABSTRACT The induction of new lung tissue after disease or trauma has the potential to save lives and transform patient outcomes. Ambystoma mexicanum, the axolotl salamander, is a classic model organism used to study vertebrate regeneration, primarily after limb amputation. While it is hypothesized that axolotls regenerate all of their tissues, exploration of lung regeneration has not been performed until now. Proliferation after lung injury was observed to be a global response, suggesting that regeneration utilizes a compensatory mechanism, in contrast to limb regeneration’s epimorphic response. ErbB signaling is crucial for the proliferative response during lung regeneration, likely through the ErbB2:ErbB4 receptor heterodimer. ErbB4 mRNA was found to be highly upregulated at both one and three weeks post amputation. Neuregulin-1p (NRG1) can induce proliferation in the lung and likely exerts molecular control over lung regeneration. Inhibition of ErbB2 was sufficient to both block regeneration and the proliferative response observed after NRG1 treatment.