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 PGE 2 signaling pathway. The current study was aimed at understanding whether COX-2 signaling plays any role in the expression of Wnt/b-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 b-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 PGE 2 pathway and Wnt/b-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.

Variation in expression and activity pattern ofmmp2andmmp9on different time scales in the regenerating caudal fin ofPoecilia latipinna

“…MMP9 inactivates IL‐1β (Ito et al, ), CXCL5 (Van den Steen et al, ) and chemokines (McQuibban et al, ) which all are important mediators of the inflammatory process. Conversely, inhibition of COX‐2 has been reported to affect the levels of gelatinase in the regenerating the tail of Hemidactylus flaviviridis (Buch et al, ). Therefore, increased level of MMP9 in our study at the transcription and translation levels in the initial wound healing phase (1–6 hpa), suggests its possible role in the regulation of inflammatory process before the initiation of tissue remodelling.…”

De Novo Transcriptome Sequencing and Analysis of Differential Gene Expression among Various Stages of Tail Regeneration in Hemidactylus flaviviridis

“…Transcripts of the major pathways governing these processes such as FGF, Shh, Wnt and TGF were also present during the transcriptome analysis. These signaling pathways control all the cellular and molecular processes required for successful regeneration in zebrafish, [ 23 , 24 , 25 ], axolotl [ 14 , 26 ], A. carolinensis [ 17 , 26 ] and H. flaviviridis [ 4 , 7 , 8 ].…”

“…Observations in our lab suggest that tail regeneration in the lizard Hemidactylus flaviviridis follows the epimorphic regeneration [ 7 ]. Epidermal cells from the periphery of the tail migrate to cover the wound surface immediately after autotomy.…”

Inhibition of Cyclooxygenase-2 Alters Craniofacial Patterning during Early Embryonic Development of Chick

“…Buch and colleagues illustrated an alteration in Wnt/β-catenin signaling under the inhibition of COX-2, which hampers the regeneration of the lizard tail [ 33 ]. The involvement of Wnt3A in the delamination of CNCC has been reported during the early embryogenesis of chicks [ 34 , 35 ].…”