OBJECTIVE Diabetic retinopathy (DR) is a major complication of both type 1 and type 2 diabetes. Recently, inflammation was found to play an important role in DR pathogenesis. But the mechanism has not been fully understood. METHODS ARPE-19 cells were cultured under normal condition and high-glucose condition, then the expressions of miR-93, XBP1s and lncRNA H19 were measured using RT-qPCR or western blots. Besides, the mRNA level of eIF2α and GRP78 and protein level of p-eIF2α and GRP78 were measured by RT-qPCR or western blots. In addition, RT-qPCR and ELISA were adopted to examine the expression and secretion of cytokine factors in these conditions. Dual-luciferase reporter gene assay was used to elucidate the binding and regulation among XBP1s, miR-93 and H19. RNA immunoprecipitation was also performed to verify the interaction between H19 and miR-93. The expressions of DNAJC3 and DNAJB9, the downstream targets of XBP1s, were detected by RT-qPCR. RESULTS We identified that H19 and XBP1s were down-regulated in ARPE-19 cells under high-glucose condition, while miR-93 was up-regulated. ER stress inducers TM and IRE1 inhibitor STF-083010 were adopted and data suggest that ER stress could be induced during high-glucose treatment. In addition, the altered expressions of miR-93, XBP1s and H19 might mediate the increased level of pro-inflammatory cytokines. Furthermore, miR-93 interacted with either lncRNA H19 or XBP1s then modulating the inflammatory processes. CONCLUSIONS H19 played an important role in regulating inflammatory processes in retinal endothelial cells under high-glucose condition through modulating miR-93/XBP1s axis.

中文翻译：

---

lncRNA H19使miR-93变质，通过XBP1s调节高血糖下视网膜上皮细胞的炎症。

目的糖尿病性视网膜病（DR）是1型和2型糖尿病的主要并发症。最近，发现炎症在DR的发病机理中起重要作用。但是该机制还没有被完全理解。方法在正常和高糖条件下培养ARPE-19细胞，采用RT-qPCR或western blot方法检测miR-93，XBP1s和lncRNA H19的表达。此外，通过RT-qPCR或蛋白质印迹法检测eIF2α和GRP78的mRNA水平以及p-eIF2α和GRP78的蛋白水平。此外，采用RT-qPCR和ELISA检测在这些条件下细胞因子的表达和分泌。使用双重荧光素酶报告基因分析来阐明XBP1s，miR-93和H19之间的结合和调控。还进行了RNA免疫沉淀以验证H19和miR-93之间的相互作用。RT-qPCR检测XBP1s的下游靶标DNAJC3和DNAJB9的表达。结果我们发现在高葡萄糖条件下ARPE-19细胞中H19和XBP1s被下调，而miR-93被上调。ER应激诱导剂TM和IRE1抑制剂STF-083010被采用，数据表明在高糖治疗​​期间可以诱导ER应激。此外，miR-93，XBP1s和H19的表达改变可能介导促炎性细胞因子水平的提高。此外，miR-93与lncRNA H19或XBP1s相互作用，然后调节炎症过程。