Low-energy electric shock ameliorates cell proliferation, morphallaxis, and regeneration via driving key regenerative proteins in earthworm and 3T3 cells.

Electric stimulation regulates many cellular processes like cell proliferation, differentiation, apoptosis and cellular migration. Despite its crucial role in regulating stem cells and regeneration, it remains underexplored in both in-vivo and in-vitro settings. In this study, Eudrilus eugeniae are subjected to electric stimulation (1.5 V) prior and after amputation and which augments regeneration up to double-time. Blocking epimorphosis using 2 M thymidine retracts regeneration kinetics to one-third but such inhibition was rescued by applying electric stimulation which propels an overactive morphallaxis pattern of regeneration. Excreting electric stimulation on control worms shows minimal impact, whereas it enhances the key regenerative proteins like VEGF, COX2, YAP, c-Myc, and Wnt3a on amputated worms. Upon blocking epimorphosis, all these key regenerative proteins are down-regulated but through electric stimulation, the cells are reprogrammed to express a triple fold of the mentioned regenerative proteins, that further promotes morphallaxis. In 3T3 cells, electric stimulation accelerates cell proliferation and migrations in 5 secs exposure and it exerts its function by overexpressing VEGF mediated by MEK1. Wnt3a expression was gradually upregulated in increasing exposure (5 and 25 secs) which aids in maintaining the stemness property. The molecular mechanism underlying regeneration capability can assist in designing novel therapeutic applications.