Elucidating Interactome Dynamics of the A2A Adenosine Receptor in the Presence of Polydeoxyribonucleotide

Polydeoxyribonucleotide (PDRN) is a tissue regeneration
substance
that resembles human DNA and is present in mammalian cells. It stimulates
physiological regeneration and metabolic activity, and the effects
of PDRN are attributed to the activation of Adenosine A2A receptors
(ADORA2A). Several previous studies have demonstrated that PDRN activates
ADORA2A, which has been shown with various models including rat fibroblasts,
human umbilical vein endothelial cells (HUVECs), and the experimental
autoimmune uveitis (EAU) model, resulting in the upregulation of angiogenesis
and growth factor. In this work, we primarily used HUVECs to study
the overall changes and dynamics of proteins related to their ADORA2A
activation. We conducted selected reaction monitoring-mass spectrometry
(SRM-MS), and we founded 374 proteins and 193 peptides demonstrating
both upregulation and downregulation in expression. We conducted gene
ontology (GO) analysis and physical network analysis and discovered
novel networks and indirect interactions of proteins related to neuronal
differentiation among the ADORA2A-associated protein. Finally, using
the AlphaFold multimer, we were able to predict interaction sites
among ADORA2A-associated proteins in the network associated with neuronal
cell differentiation. Specifically, we predicted five interaction
sites between ADORA2A and Neurotrophic Receptor Tyrosine Kinase 1
(NTRK1), forming the edge. Thus, we provided indicators for further
research using ADORA2A present in a robust network and highlighted
the potential of PDRN to impact neuronal differentiation.