Inhibition of Cyclooxygenase-2 Alters Wnt/β-Catenin Signaling in the Regenerating Tail of Lizard Hemidactylus flaviviridis

ABSTRACT

Epimorphic regeneration in vertebrates involves the restoration of lost tissue or organs through the formation of a regeneration blastema and occurs through a complex interaction of a number of molecular signaling pathways. Of the many effectors of successful tail regeneration in the lizard Hemidactylus flaviviridis, one crucial pathway is the cyclooxygenase-2 (COX-2) mediated PGE2 signaling pathway. The current study was aimed at understanding whether COX-2 signaling plays any role in the expression of Wnt/β-Catenin signaling components during regenerative outgrowth in H. flaviviridis. Etoricoxib—selective inhibitor of the inducible isoform of COX-2—was administered to lizards orally. We tested the expression of β-Catenin during wound epidermis and blastema stages in the regenerating tail and found a reduction in its expression in response to drug treatment. Further, it was observed that the expression of canonical Wnt ligands was greatly altered due to COX-2 inhibition. Our results provide evidence of a cross-talk between the COX-2 induced PGE₂ pathway and Wnt/β-Catenin signaling in the regenerating lizard tail. An understanding of the interaction among various signaling pathways will help elucidate the mechanism underlying epimorphosis in lizards, the only amniotes capable of appendage regeneration.