Hydrogen peroxide is necessary during tail regeneration in juvenile axolotl

Hydrogen peroxide (H₂ O₂ ) is a key reactive oxygen species (ROS) generated during appendage regeneration among vertebrates. However, its role during tail regeneration in axolotl as redox signaling molecule is unclear.

Treatment with exogenous H₂ O₂ rescues inhibitory effects of apocynin-induced growth suppression in tail blastema cells leading to cell proliferation. H₂ O₂ also promotes recruitment of immune cells, regulate the activation of AKT kinase and Agr2 expression during blastema formation. Additionally, ROS/H₂ O₂ regulates the expression and transcriptional activity of Yap1 and its target genes Ctgf and Areg.

These results show that H₂ O₂ is necessary and sufficient to promote tail regeneration in axolotls. Additionally, Akt signaling and Agr2 were identified as ROS targets, suggesting that ROS/H₂ O₂ is likely to regulate epimorphic regeneration through these signaling pathways. In addition, ROS/H₂ O₂ -dependent-Yap1 activity is required during tail regeneration.