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

• Main Authors: Yo-Chen Chang (Author), Yuh-Shin Chang (Author), Ming-Chu Hsieh (Author), Horng-Jiun Wu (Author), Meng-Hsien Wu (Author), Chia-Wei Lin (Author), Wen-Chuan Wu (Author), Ying-Hsien Kao (Author)
• Format: Book
• Published: Elsevier, 2016-12-01T00:00:00Z.
• Subjects: article
• Online Access: Connect to this object online.

Summary

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.

Item Description

1347-8613
10.1016/j.jphs.2016.11.002