XB-ART-61789
Free Radic Biol Med
2026 Apr 01;250:411-421. doi: 10.1016/j.freeradbiomed.2026.04.001.
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Divergent redox states define regenerative outcomes between salamanders and Xenopus.
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Salamanders possess the extraordinary ability to regenerate limbs throughout life, whereas Xenopus lose this capacity after metamorphosis, producing only rudimentary "spikes" after limb amputation. Here, we investigate the underlying mechanisms governing these distinct regenerative outcomes by focusing on the role of endogenous oxygen consumption and reactive oxygen species (ROS) dynamics. The gene expression, oxygen consumption and redox state analysis indicated that Xenopus undergo intense oxidative metabolism and DNA damage during metamorphosis, which was conspicuously absent in salamanders. Environmental hyperoxic conditions significantly impede early blastema formation and disrupt patterning in salamanders, while hypoxia accelerates limb regeneration in Xenopus tadpole. Furthermore, scavenging ROS in the regeneration-incompetent Xenopus promotes limb regeneration and patterning. These findings identify intrinsic oxidative stress as a critical barrier to regeneration and suggest that reducing oxidative stress could enhance regenerative outcomes.
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Species referenced: Xenopus laevis
Genes referenced: atg9a atp6v0e1 atp6v1f axin2 bcl2l13 cops6 cox11 cox17 ern1 fgf8 gabarapl2 hoxa2 hoxd11 map1lc3a mapk11 mcl1 nfkbia pax7 pcna phb2 pold3 rnf169 shh smc2 smc4 smg1 sqstm1 tbc1d15 tbc1d17
GO keywords: double-strand break repair via homologous recombination
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