All-trans retinoic acid suppresses the adhering ability of ARPE-19 cells via mitogen-activated protein kinase and focal adhesion kinase

This study investigated the signaling mechanism underlying the anti-adhesive effect of all-trans retinoic acid (atra) on retinal pigment epithelial arpe-19 cells. adhesion kinetics with or without atra treatment were profiled by adhesion assay. surface coating with type iv collagen,fibronectin,laminin,but not type i collagen,significantly enhanced adhesion and spreading of arpe-19 cells,while atra at subtoxic doses (ranging from 10–7 to 10–6 m) profoundly suppressed the extracellular matrix-enhanced adhesion ability. cell attachment on fn activated pi3k/akt and mapk cascades,whereas atra pretreatment blunted the early phosphorylation of akt and mapk signaling mediators including p38 mapk,jnk1/2,and erk1/2. mechanistically,signaling blockade with selective kinase inhibitors demonstrated that all mapk pathways were involved in the anti-adhesive effect of atra,whereas the pi3k inhibitor treatment significantly potentiated the atra-suppressed rpe cell adhesion. moreover,atra treatment did not affect intracellular f-actin distribution,but remarkably reduced focal adhesion kinase (fak) expression and its nuclear localization during arpe-19 cell attachment. in conclusion,atra suppresses the adhering ability of arpe-19 cells at least in part through mapk and fak pathways. signaling blockade with pi3k inhibitor could be regarded as an alternative modality for treating proliferative vitreoretinopathy. © 2016 the authors