Dev Biol 2024 Mar 16;519:65-78. doi: 10.1016/j.ydbio.2024.12.009.

Quantitative proteomics of regenerating and non-regenerating spinal cords in Xenopus.

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Spinal cord injury in humans is a life-changing condition with no effective treatment. However, many non-mammalian vertebrates can fully regenerate their spinal cord after injury. Frogs such as Xenopus can regenerate the spinal cord at larval stages, but lose this capacity at metamorphosis. This makes them ideal models to elucidate molecular pathways underlying regenerative capacity by comparing responses to spinal cord injury in regenerative (R) and non-regenerative (NR) stages of the same species. Here we use quantitative proteomics with Isobaric Tags for Relative and Absolute Quantification (iTRAQ) followed by Ingenuity Pathway Analysis (IPA) to identify functions and pathways that were differentially regulated after spinal cord injury between R and NR stages in Xenopus laevis. We find that many embryonic pathways of neuronal development are re-activated following SCI at the R but not at the NR stage. This is accompanied by the upregulation of regulatory proteins controlling transcription and translation at the R stage, but their downregulation at the NR stage. Conversely, lipid hydrolysis and uptake as well as mitochondrial oxidative phosphorylation is downregulated at the R, but upregulated at the NR stage. Taken together this suggests that dysregulation of lipid homeostasis and augmentation of oxidative stress play a key role in the loss of regenerative capacity of the spinal cord after metamorphosis. In identifying new factors regulating regenerative capacity in the vertebrate spinal cord, our findings suggest new potential therapeutic targets for promoting neural repair in the injured adult mammalian spinal cord.

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Species referenced: Xenopus laevis
Genes referenced: actr1a ak2 alb aldob aldoc amph anp32b apoa1 apoc2 arrb1 arsa atp5f1b atp5pd ccbe1 cirbp ckm ckmt1b cnbp cnp cox6b1 crmp1 ctsb ctsz dbn1 ddah2 des dlst dnpep dpysl2 dpysl3 dpysl5 eci1 eno1 fabp3 fabp7 fetub fkbp1a gapdh glud1 hmgb1 hmgb2 hmgb3 hmgn1 hpd hspa8 hspd1 hspe1 idh1 idh2 idh3a itpr1 lamtor3 lmnb2 lsp1 marcks marcksl1 mbp mrps16 ncam1 ncl nefm npm1 ntm nudc nup54 ocm pa2g4 pabpc1 pde6d pdia3 pgk1 pgm1 pkm plp1 ppib ppp2cb prox1 prph psmb4 ptma ptpra ran ring1 rpia rpl10 rpl24 rpl32 rpl3l rpl7 rps18 rps29 rps3a rps4x rps6 rps9 serpine2 shmt1 sncb sncg sptan1 srsf7 syn1 tkt tmsb10 tmsb4x tpm1 tpm4 tuba1a tubb2b txn2 txnl1 vamp2 vcp ybx1 ywhae ywhaz
GO keywords: regeneration