Djvcp regulates planarian regeneration and homeostasis via coordinating cell proliferation and apoptosis

Valosin-containing protein (VCP), a conserved AAA + ATPase, plays central roles in protein quality control, cell cycle regulation, and cell survival, but its function in planarian regeneration has not been explored. Here, we identified and characterized a VCP homolog in Dugesia japonica , termed Djvcp , which exhibits strong evolutionary conservation. Expression profiling revealed that Djvcp is predominantly expressed in parenchymal tissues and regenerative blastema. Functional studies demonstrated that Djvcp knockdown resulted in severe regenerative defects, including failed blastema formation, incomplete reconstitution of neural, gut, and pharyngeal tissues, compromised locomotor recovery, and ultimately organismal death. Mechanistically, Djvcp depletion markedly suppressed neoblast proliferation while enhancing apoptosis during early regeneration and homeostasis. Integrated transcriptomic profiling and experimental analyses further revealed that Djvcp depletion was associated with impaired protein homeostasis and altered PI3K-Akt signaling activity. Moreover, loss of Djvcp caused progressive tissue degeneration and lethality in intact animals, indicating an essential role in tissue homeostasis. Together, these findings provide novel insights into the conserved functions of Djvcp in planarian regeneration and tissue maintenance.