Basic regulatory effects and clinical value of metalloproteinase-14 and extracellular matrix metalloproteinase inducer in diabetic retinopathy

Abstract

This study examined the basic regulatory effects and clinical value of metalloproteinase-14 and extracellular matrix metalloproteinase inducer in diabetic retinopathy. Seventy-four patients with diabetic retinopathy (study group/diabetic retinopathy (DR) group) and 48 healthy people (control group) were included in this study. Venous blood of subjects in the two groups was collected and the plasma levels of EMMPRIN, MMP-14, VEGF, and MMP-9 were determined by enzyme-linked immunosorbent assay. The value of applying plasma EMMPRIN and MMP-14 for predicting the prognosis of DR was evaluated using a receiver operating characteristic (ROC) curve with a 1-year follow-up. Human umbilical vein endothelial cells (HUVECs) were cultured in high-glucose conditions. EMMPRIN and MMP-14 mRNA levels were determined by RT-qPCR, EMMPRIN and MMP-14 protein levels were determined by Western blotting, apoptosis was determined by flow cytometry, and the level of angiogenesis was recorded. The levels of EMMPRIN and MMP-14 in the DR group were increased compared with those in the control group. Plasma EMMPRIN was positively correlated with plasma MMP-9 and plasma VEGF, and its area under the curve (AUC) for predicting 1-year adverse outcome of DR was 0.676. Plasma MMP-14 was also positively correlated with plasma MMP-9 and plasma VEGF, and its AUC for predicting 1-year adverse outcome of DR was 0.650. EMMPRIN and MMP-14 were upregulated in high-glucose-induced HUVECs. Downregulation of EMMPRIN resulted in downregulation of MMP-14, and downregulation of MMP-14 and EMMPRIN resulted in decreased apoptosis and angiogenesis of HUVECs. These findings suggest that EMMPRIN promotes endothelial cell apoptosis and angiogenesis in DR through MMP-14, and that plasma EMMPRIN and MMP-14 can help predict the short-term prognosis of DR.