PGE2 facilitates tail regeneration via activation of Wnt signaling in Gekko japonicus.

Abstract

Tail regeneration is a distinguishing feature of lizards; however, the mechanisms underlying tail regeneration remain elusive. Prostaglandin E2 (PGE2) is an arachidonic acid metabolite that has been extensively investigated in the inflammatory response under both physiological and pathological conditions. PGE2 also act as a regulator of hematopoietic stem cell homeostasis by interacting with Wnt signaling molecules. The present study aims to identify the effects of PGE2 on tail regeneration and the molecular mechanisms behind it. We initially found that PGE2 levels increased during the early stages of tail regeneration, accompanied by the up-regulated expression of cyclooxygenase 1 and cyclooxygenase 2. Next, we demonstrated that reduced PGE2 production leads to the retardation of tail regeneration. Subsequent experiments demonstrated that this effect is likely mediated by Wnt signaling, which proposing that the activation of the Wnt pathway is essential for the initiation of regeneration. The results showed that inhibition of PGE2 production could suppress Wnt activation and inhibit the proliferation of both epithelial and blastema cells. Furthermore, our findings indicated that forced activation of Wnt signaling could rescue the inhibitory effect of Cox antagonist on regeneration, suggesting a positive role of PGE2 on tail regeneration via a non-inflammatory mechanism.