%0 Journal Article
%T ARPE-19-derived VEGF-containing exosomes promote neovascularization in HUVEC: the role of the melanocortin receptor 5
%A Clara Di Filippo
%A Francisco Javier Romero
%A Javier Sancho-Pell¨²z
%A Jorge Miguel Barcia
%A Lorena Vidal-Gil
%A Mar¨ªa Oltra
%A Michele D¡äAmico
%A Natalia Mart¨ªnez-Gil
%A Rosa Maisto
%A Settimio Rossi
%J Archive of "Cell Cycle".
%D 2019
%R 10.1080/15384101.2019.1568745
%X ARPE-19 retinal pigment epithelial cells cultured in a medium containing 35 mM D-glucose led to an augmented ROS formation and release of vascular endothelial factor (VEGF)-containing exosomes compared to ARPE-19 cells cultured in a medium containing 5 mM D-glucose (standard medium). Exposing these cells to the melanocortin 5 receptor agonist (MCR5) PG-901 (10£¿10M), for 9 d reduced ROS generation, the number of exosomes released and their VEGF content. In contrast, incubating the cells with the melanocortin receptor MCR1 agonist BMS-470539 (10£¿5 M) or with the mixed MCR3/4 agonist MTII (0.30 nmol) did not produce any significant decrease in ROS levels. ARPE-19-derived VEGF-containing exosomes promoted neovascularization in human umbilical vein endothelial cells (HUVEC), an effect that was markedly reduced by PG-901 (10£¿10M) but not by the MCR3/4 agonist MTII (0.30 nmol) or the MCR1 agonist BMS-470539 (10£¿5 M). The MCR5-related action in the ARPE-19 cells was accompanied by the increased expression of two coupled factors, cytochrome p4502E1 (CYP2E1) and nuclear factor kappa b (Nf-¦ÊB). These are both involved in high glucose signalling, in ROS generation and, interestingly, were reduced by the MCR5 agonist in the ARPE-19 cells. Altogether, these data suggest that MCR5 is a modulator of the responses stimulated by glucose in ARPE-19 cells, which might possibly be translated into a modulation of the retinal pigment epithelium response to diabetes in vivo
%K Diabetes
%K melanocortin receptors
%K oxidative stress
%K vasculogenesis
%K exosomes
%U https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6422460/