The effect of beta-adrenergic stimulation in the expression of the urokinase plasminogen activator receptor in bone marrow mesenchymal stem cells

Abstract

BackgroundThe migration of bone marrow mesenchymal stem cells (BMMSCs) from bone marrow (BM) to the damaged sites is the first step in regenerative medicine. BMMSCs express all urokinase system components include; urokinase plasminogen activator (uPA), uPA receptor (uPAR), and plasminogen activator inhibitor-1 (PAI-1) that are shown to affect BMMSCs migration. Also, it has been reported that the signaling of the β-adrenergic receptors (β-AdR) on BMMSCs increase their mobilization from bone marrow to the periphery. In this study, we surveyed the expression of β-AdRs in BMMSCs and the role of β-AdR stimulation using isoproterenol (β-Adrenergic agonist) in the expression of urokinase plasminogen activator receptor (uPAR) in BMMSCs. MethodsWe characterized BMMSCs isolated from bone marrow aspiration of two patients by their surface markers. The expression of β-AdRs, including β1-AdR, β2-AdR, and β3-AdR in MSCs were assayed using RT-PCR. BMMSCs were treated with isoproterenol, and uPAR mRNA expression was measured in three time-points (1, 3, and 5 h after adding isoproterenol) using qRT-PCR. ResultsThe flow cytometry analysis result proved the specific characters of MSCs. The expression of uPAR increased in all three time-points of isoproterenol treatment, but a significant increase in uPAR mRNA was seen in MSCs treated 5 h with isoproterenol, compared to the untreated MSCs and also MSCs treated less than 5 h (1 and 3 h). ConclusionAccording to the results, beta-adrenergic signaling can increase the expression of uPAR in MSCs, which might facilitate their mobilization into the peripheral blood.