Adenosine and Cordycepin Accelerate Tissue Remodeling Process through Adenosine Receptor Mediated Wnt/?-Catenin Pathway Stimulation by Regulating GSK3b Activity

Adenosine is a cellular metabolite with diverse derivatives that possesses wide range of physiological roles. We investigated the molecular mechanisms adenosine and cordycepin for their promoting effects in wound-healing process. The mitochondrial energy metabolism cell proliferation markers, cAMP responsive element binding protein 1 (CREB1) Ki67, were enhanced by cultured dermal fibroblasts. stimulated receptor signaling via elevated cAMP. phosphorylation mitogen-activated kinase (MEK) 1/2, mammalian target rapamycin (mTOR) glycogen synthase 3 beta (Gsk3b) Wnt genes such as bone morphogenetic (BMP) 2/4 lymphoid enhancer factor (Lef) activated. gene expression was abrogated A2A A2B inhibitors, ZM241385 PSH603, A (PKA) inhibitor H89, indicating involvement A2A, PKA. As result Wnt/?-catenin pathway activation, secretion growth factors insulin-like (IGF)-1 transforming (TGF?) increased, previously reported to facilitate wound healing In addition, vitro fibroblast migration also demonstrating possible roles facilitating conclusion, our data strongly demonstrate stimulate through activation receptor, possibly tissue remodeling process suggest therapeutic potential treating skin wounds.