Tissue Eng Regen Med.  2024 Feb;21(2):353-366. 10.1007/s13770-023-00599-w.

Understanding the Multi-Functional Role of TCTP in the Regeneration Process of Earthworm, Perionyx excavatus

• Rajagopalan K
• Christyraj JDS
• Chelladurai KS
• Das P
• Mahendran K
• Nagarajan L
• Gunalan S

• KMID: 2553265
• DOI: http://doi.org/10.1007/s13770-023-00599-w

Abstract

BACKGROUND
Regeneration is a highly complex process that requires the coordination of numerous molecular events, and identifying the key ruler that governs is important to investigate. While it has been shown that TCTP is a multifunctional protein that regulates cell proliferation, differentiation, apoptosis, anti-apoptosis, stem cell maintenance, and immune responses, but only a few studies associated to regeneration have been reported. To investigate the multifunctional role of TCTP in regeneration, the earthworm Perionyx excavatus was chosen.
METHODS
Through pharmacological suppression of TCTP, amputation, histology, molecular docking, and western blotting, the multi-function role of TCTP involved in regeneration is revealed.
RESULTS
Amputational studies show that P. excavatus is a clitellum-independent regenerating earthworm resulting in two functional worms upon amputation. Arresting cell cycle at the G1/S boundary using 2 mM Thymidine confirms that P. excavatus execute both epimorphosis and morphallaxis regeneration mode. The pharmacological suppression of TCTP using buclizine results in regeneration suppression. Following the combinatorial injection of 2 mM Thymidine and buclizine, the earthworm regeneration is completely blocked, which suggests a critical functional role of TCTP in morphallaxis. The pharmacological inhibition of TCTP also suppresses the key proteins involved in regeneration: Wnt3a (stem cell marker), PCNA (cell proliferation) and YAP1 (Hippo signalling) but augments the expression of cellular stress protein p53.
CONCLUSION
The collective results indicate that TCTP synchronously is involved in the process of stem cell activation, cell proliferation, morphallaxis, and organ development in the regeneration event.

Keyword

TCTP; Buclizine; Wnt3a; p53; Hippo signaling