Abstract
PIN1, which belongs to a family of prolyl isomerases, specifically binds to phosphorylated Ser/Thr-pro motifs to catalytically regulate the post-phosphorylation conformation of its substrates. This study aimed to investigate the importance of Pin1 expression in human dental pulp cells (hDPCs) to understand the involvement of Pin1 in the regulation of P2Y1 and the activation of ADP-mediated P2Y1 signaling. This study found that the protein levels of P2Y1 gradually decreased after the onset of cell recovery following heat stress. Interestedly, hDPC migration significantly decreased during the recovery period. An in vitro study revealed that the silencing of PIN1 by siRNA or the pharmacologic inhibition of its activity decreased the migration of P2Y1 and P2Y1 expression in these cells. In addition, we found that Pin1 directly interacts with S252 of P2Y1 and that its binding stabilizes the P2Y1 protein to increase migration activity. These results strongly suggest that Pin1 mediates cell migration by stabilizing P2Y1 and that the Pin1/P2Y1 signaling pathways might serve as a novel mechanism of cell migration progression in hDPCs.
Highlights
Human dental pulp cells are multipotent cells with the potential to differentiate into a variety of cell types, including osteoblasts, chondrocytes, adipocytes, endothelial cells, neural progenitor cells, and myotubes [1, 2]
Our findings demonstrate that Pin1 stimulates the P2Y1-mediated migration of in Human dental pulp cells (hDPCs) by stabilizing the P2Y1 protein and that Pin1 directly interacts with phosphorylated S252 in P2Y1, thereby regulating the ADP-stimulated migration activity of hDPCs
To determine whether thermal stress influences the expression of P2Y1 receptors in hDPCs, we performed RT-PCR using specific oligonucleotides against each of the P2Y1 family genes
Summary
Human dental pulp cells (hDPCs) are multipotent cells with the potential to differentiate into a variety of cell types, including osteoblasts, chondrocytes, adipocytes, endothelial cells, neural progenitor cells, and myotubes [1, 2]. Various research groups have reported a role for adenosine nucleotide signaling through P2Rs in progenitor cell migration [7, 8]. Purinergic signaling modulates several biological functions in human bone marrow stem cells (hMSCs), including migration [7, 9, 10]. It has been shown that human hematopoietic stem cells express several subtypes of functional P2XRs and P2YRs and that the stimulation of CD34+ cells by extracellular nucleotides improves their clonogenic capacity and migration in immunodeficient mice [11]. The migration of mouse glial progenitor cells has been shown to be regulated by the release of intracellular Ca2+, which is driven by ATP-induced P2Y1 activation [12]. The P2Y1 receptor is active in inflammatory responses and is associated with the migration of endothelial cells through activation of the small GTPase Rac, reinforcing its relevance as an attractive target for new cardiovascular therapeutics [14, 15]
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