Abstract
Background: Regeneration process orchestrates various bio-physiology mechanisms for wound healing such as inflammation immune response for preventing infection, proliferation for blastema accumulation, differentiation and dedifferentiation of cells for tissue development. Zebrafish is an important vertebrate organism for modeling and has many advantages includes its strong regenerative capability on heart, fins, and central nervous system, genome similarity to human, high productive rate and low maintenance costs. Using zebrafish as the model to study regeneration mechanism becomes popular. Result: Based on time-course microarray data of four zebrafish-organs wound healing experiments includes heart, brain, fin and retina, we constructed four regenerative PPI networks, which captures activated pathways based on experiment data through applying AIC to select significant PPIs. We extracted core proteins (intersection set) and specific proteins (relatively complement set) and use both GO biological function and pathway classification on these proteins sets including TGF-β signaling for core proteins, integrins for heart specific proteins, Wnt signaling for brain specific proteins, angiogenesis for fin specific proteins, and Bdnf for retina specific proteins. To investigate the underlying mechanism of organ regeneration, we proposed a five-step blastema model and applied our observation from the PPI networks to uncover regeneration strategy of zebrafish. In result, TGF-β signaling in core proteins participates variety biological function and was observed in each step in blastema model. Integrins, FGF and PDGF co-regulate binding affinity for fibrin and fibrinogen for rapid hemostasis through mediation of integrins during heart injury. Wnt signaling mediates growth and differentiation of neuron stem cells for brain and fin in differentiation and pattern formation step. And Bdnf prevents retinal neuron from secondary damage and strengthens the survival ability at the injury response step. Conclusion: Via our analysis of all four zebrafish regenerative PPI networks, we investigated the underlying strategy of zebrafish organ regeneration. With a better understanding of regeneration strategy for zebrafish, we hope to advance therapeutic and drug design for regenerative medicine.