Molecular dynamics and spatial response of proliferation and apoptosis in wound healing and early intestinal regeneration of sea cucumber Apostichopus japonicus

The sea cucumber, Apostichopus japonicus, exhibits significant regenerative capabilities. To ensure survival and reduce metabolic costs under adverse conditions, A. japonicus can expel intestine, respiratory trees and other internal organs. It takes only 14 days to regenerate a fully connected, lumen-containing intestine. Despite numerous reports characterizing the cellular events in intestinal regeneration, limited investigation has been conducted on the molecular events that occur during wound healing and the initial stages of regeneration after evisceration. Here, we identified differentially expressed genes (DEGs) during wound healing (6 h post-evisceration, Aj6hpe) and early intestinal regeneration (Aj1dpe, Aj3dpe, Aj7dpe). Cell proliferation and apoptosis were detected by EdU and TUNEL assays, respectively. Results demonstrated that calcium ion and neuroactive ligand-receptor interaction were involved in the transmission of injury signals from evisceration to Aj1dpe. The main events occurring in the wound healing and early regeneration process were autophagy, apoptosis, dedifferentiation, migration and shutdown of feeding. Cell proliferation was primarily observed during the lumen formation stage. Maximal number of apoptotic cells were found during wound healing stage (6 hpe - 1 dpe). Consequently, the immune response is mainly mobilized by neural regulation after evisceration. Our findings bridge the gap between evisceration and regeneration, illuminating the molecular events that mediate damage response and initiate regeneration. This study significantly advances our understanding of the mechanisms underlying intestinal regeneration.