Knockdown of MALAT1 attenuates high-glucose-induced angiogenesis and inflammation via endoplasmic reticulum stress in human retinal vascular endothelial cells.

Diabetic retinopathy (DR) is one of the most severe complications of diabetes mellitus, and retinal endoplasmic reticulum stress (ERS) plays an important role in the pathogenesis of DR. However, the exact mechanisms by which ERS mediates DR remain unclear. In this study, human retinal vascular endothelial cells (RVECs) were cultured in high-glucose (HG) medium to mimic the environment of DR. The expression of long non-coding RNA (lncRNA)-metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) was determined by quantitative real time PCR. ERS markers (glucose-regulated protein 78 [GRP78] and C/EBP homologous protein [CHOP]) were measured by immunofluorescence and western blotting. Cell viability was analyzed by the CCK-8 assay. The angiogenesis of RVECs was evaluated by tube formation assays. The levels of pro-inflammation cytokines TNF-α and IL-6 in RVECs were determined by ELISA assays. We found that exposure to HG levels upregulated MALAT1 and GRP78 expression in RVECs. While, GRP78 overexpression strengthened CHOP expression, cell proliferation suppression, capillary morphogenesis and inflammation in HG-treated RVECs. Importantly, knockdown of MALAT1 reversed HG-induced cell proliferation suppression, inhibited capillary morphogenesis, and inflammation in RVECs, and those effects were reversed by GRP78 overexpression. These results suggest that MALAT1 promotes HG-induced angiogenesis and inflammation in RVECs by upregulating ER stress, and might be target for treating DR.