Hydrogen peroxide is necessary during tail regeneration in juvenile axolotl

Abstract

Background Hydrogen peroxide (H2O2) 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. Results Treatment with exogenous H2O2 rescues inhibitory effects of apocynin‐induced growth suppression in tail blastema cells leading to cell proliferation. H2O2 also promotes recruitment of immune cells, regulate the activation of AKT kinase and Agr2 expression during blastema formation. Additionally, ROS/H2O2 regulates the expression and transcriptional activity of Yap1 and its target genes Ctgf and Areg. Conclusions These results show that H2O2 is necessary and sufficient to promote tail regeneration in axolotls. Additionally, Akt signaling and Agr2 were identified as ROS targets, suggesting that ROS/H2O2 is likely to regulate epimorphic regeneration through these signaling pathways. In addition, ROS/H2O2‐dependent‐Yap1 activity is required during tail regeneration.

An early Shh-H2O2 feedback loop controls the progression of the regenerative program during adult zebrafish fin regeneration

“…It was first demonstrated that during the very early phase of wound healing in the zebrafish larval tail fin, a Duox-dependent gradient of H2O2 is generated within 3 min at the wound margin, peaks at 20 min and is required for the recruitment of distant leukocytes 39 . Members of the NOX family were subsequently shown to be involved in regeneration per se, as is the case in the adult zebrafish caudal fin 13,22 and heart 14 , gecko tail 15 and juvenile axolotl or Xenopus tadpole tail 40,41 .…”

Evolutionarily divergent mTOR remodels the translatome to drive rapid wound closure and regeneration

“…While excessive levels of ROS are detrimental to cellular homeostasis, previous studies show that at a certain threshold ROS act as important activators of signaling pathways. The translational control of ROS regulators is interesting as their activation at sites of injury is an important facet of regeneration in a variety of species, including zebrafish, frogs, planaria, and axolotls [27][28][29][30][31][32][33] . Selective translation of these proteins suggests that induction and a delicate balance of ROS during wound healing and regeneration is a part of a heretofore unexplored and tightly regulated post-transcriptional regulatory process.…”

“…Our polysome sequencing, detected translational activation of peroxiredoxin, an important antioxidant, within 24 hpa. Previous studies showed that sustained accumulation of ROS is critical for tissue regeneration [29][30][31]33 . In contrast, high levels are toxic, therefore cells must carefully orchestrate a balance of ROS production 51 .…”

Ambystoma mexicanum, a model organism in developmental biology and regeneration: a colombian experience

“…However, the time in which these stages occur differs from those of smaller animals with approximately 2-3 cm (Echeverri et al, 2001). Currently, in our laboratory, several ongoing projects are evaluating the effect of some signaling molecules involved in the regeneration of this structure such as reactive oxygen species (ROS) and their interaction with other signaling pathways, using chemical inhibitors that are placed directly on the aquatic environment (Carbonell et al, 2021). Given the location of the tail, its shape, and the relatively easy surgical access to the tissue, it allows tools such as electroporation of plasmids and other constructs to be quite viable (Echeverri and Tanaka, 2003).…”