Demethoxycurcumin inhibits the cell migration and MMP-2 expression in human retinal pigment epithelial cells by targeting the STAT-3 pathway

Abstract

Proliferative vitreoretinopathy (PVR) involves retinal pigment epithelium (RPE) cell proliferation and migration and leads to tractional retinal detachment. Demethoxycurcumin (DMC), a curcuminoid, has anti-inflammatory and anti-tumour properties. However, whether DMC affects the migration of RPE cells and the molecular mechanism of human PVR remains unclear. The aim of the current study was to investigate the effects of DMC on the inhibition of migration and proteinase expression of human ARPE-19 cells. Herein, we provided molecular evidence associated with PVR prevention through DMC by inhibiting ARPE-19 cell migration. We performed gelatin zymography, Western blot and RT-PCR and respectively found that DMC is sufficient to reduce matrix metalloproteinase-2 (MMP-2) activity, protein level and mRNA expression. DMC suppressed the nuclear levels of transcriptional factors specificity protein 1 and c-Fos, which are involved in the modulation of the transcriptional activation of the MMP-2 gene. DMC also inhibited STAT-3 phosphorylation in ARPE-19 cells. Selective STAT-3 induction by a STAT-3 activator, colivelin, reverted MMP activity and protein expression and cell migration, which were reduced in response to DMC. The results proved the inhibitory effect of DMC on RPE cell migration and MMP-2 expression by the down-regulation of the STAT-3 signalling pathway.