Apelin induces the proliferation, migration and expression of cytoskeleton and tight junction proteins in human RPE cells via PI-3K/Akt and MAPK/Erk signaling pathways.

Diabetic retinopathy is major cause of vision loss during working age. Breakdown of blood-retinal barrier is an early event in pathogenesis of DR. RPE is the major part of outer BRB. Apelin, an endogenous ligand of APJ, mediates angiogenesis. Our previous study showed that apelin induced proliferation, migration, and collagen I mRNA expression in human RPE cells via PI-3K/Akt and MAPK/Erk signaling pathways. Now we investigate the connection between apelin and RPE in vascular permeability of diabetic retinopathy and its working mechanism. Our study showed that apelin promotes the proliferation, migration and expression of cytoskeleton and tight junction proteins in human RPE cells using MTS and transwell chamber assay. Apelin also activated the expression of PI-3K/Akt and MAPK/Erk signaling pathways proteins, such as PLCγ1, p38, Akt and Erk phosphorylation in RPE cells using laser scanning confocal detection, PCR and western blot. Pretreatment with the inhibitor of apelin receptor APJ, F13A, abolished the apelin-induced activations of the proliferation, migration and expression of cytoskeleton, tight junction and PI-3K/Akt and MAPK/Erk signaling pathways proteins in human RPE cells. It suggested that apelin as a promoter in retinal vascular permeability during early stage of DR, provides further evidence for neurovascular crosstalk in pathogenesis of DR, which may offer a new target in early prevention and treatment of DR.