EN
TÜRKÇE
Oral Presentation - 110
Mechanism of Propranolol-Mediated Inhibition of Infantile Hemangioma Endothelial Cell Proliferation via APLN/APJ Signaling
Qiang Chen 1, Yimin Xie 1, Sili Ni 2, Hua Wang 2
1 Chongqing University Three Gorges hospital
2 Children's Hospital of Chongqing Medical University
Objective
To investigate the role of the APLN/APJ signaling axis in the therapeutic mechanism of propranolol for infantile hemangioma.
Methods
Primary human umbilical vein endothelial cells (HUVECs), CHO/APJ/Gα15, and U2OS/Apelin/Arrestin cell lines were used as tool cells. HUVECs were divided into a control group and a group treated with 10 µM propranolol. The stability of APLN mRNA was assessed using actinomycin D treatment, and the promoter activity of APLN was evaluated via dual-luciferase reporter assay. Molecular docking was employed to predict the binding mode between propranolol and APJ. Surface plasmon resonance (SPR) was used to detect their physical binding capacity. Functional assays were performed to assess β-arrestin2 recruitment, calcium flux, and cAMP activation following propranolol-APJ binding, thus comprehensively evaluating the effects from binding prediction, physical interaction, to downstream functional activation.
Results
(1) Propranolol reduced the stability of APLN mRNA;
(2) Propranolol inhibited the promoter activity of APLN;
(3) Molecular docking suggested that propranolol can bind to APJ;
(4) SPR experiments confirmed the physical interaction between propranolol and APJ, albeit with weak binding affinity;
(5) Functional assays showed that propranolol binding to APJ did not activate downstream signaling pathways including calcium influx, cAMP production, or β-arrestin2 recruitment.
Conclusion
Propranolol reduces APLN transcription by inhibiting promoter activity and decreasing mRNA half-life. Although propranolol can physically bind to APJ, the binding affinity is weak and insufficient to activate downstream signaling. These findings suggest that propranolol regulates the APLN/APJ axis mainly by decreasing the expression of the ligand APLN, thereby contributing to its therapeutic effect in infantile hemangioma.