Conclusions
This study highlights NCOA7 as a potential target for therapeutic intervention to mediate EndMT via ROS species production.
Objective
Overproduction of reactive oxygen species (ROS) has been implicated in inflammatory activities and tumorigenesis in oral submucous fibrosis (OSF). Nuclear receptor coactivator 7 (NCOA7) is capable of regulating cellular responses to ROS. The aim of this study was to investigate the expression of NCOA7 in endothelial cells and the role of NCOA7 in areca nut-induced endothelial-to-mesenchymal transition (EndMT). Study design: Immunohistochemistry and immunofluorescence were used to detect the expression of NCOA7 in endothelia. Human umbilical vein endothelial cells (HUVECs) were treated with various dosages of arecoline (0, 5, 10, 20 μg/mL); then NCOA7 expression, the correlation of NCOA7 with EndMT, and the potential signaling were analyzed by using small interfering RNA (siRNA) transfection, reverse transcription polymerase chain reaction, Western blotting, and flow cytometry.
Results
NCOA7 was significantly elevated in OSF tissues, as detected with immunohistochemistry and immunofluorescence. After arecoline treatment, NCOA7 expression and EndMT were induced in HUVECs. Transfection of HUVECs with si-NCOA7, which reduced 73% of NCOA7 expression, aggravated the arecoline-induced EndMT process. Inhibition of ROS markedly, but not completely, reverses this arecoline-induced EndMT in si-NCOA7 cells. Conclusions: This study highlights NCOA7 as a potential target for therapeutic intervention to mediate EndMT via ROS species production.