Music College of Jiangxi Normal University, Nanchang 330022, China.
Department of Ophthalmology, The Second Affiliated Hospital of Nanchang University, Nanchang 330006, China.
Comput Math Methods Med. 2022 Oct 17;2022:1755945. doi: 10.1155/2022/1755945. eCollection 2022.
This study is aimed at screening for differentially expressed long noncoding RNAs (lncRNAs) associated with the pathogenesis of diabetic retinopathy and verifying the role of lncZNRD1 in high glucose-induced injury of retinal microvascular endothelial cells. The retinal tissues of normal and diabetic rats were collected for high-throughput sequencing of differentially expressed lncRNAs. Retinal microvascular endothelial cells were treated with 50 mM glucose for 4 h, 8 h, 24 h, 48 h, and 72 h. Our results showed that compared with the control group, there were 736 differentially expressed lncRNAs in the retina tissue of the model group, including 226 upregulated genes and 736 downregulated genes. Based on the differentially expressed lncRNAs, Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis indicated that the ErbB signaling pathway, transforming growth factor- (TGF-) signaling pathway, PI3K - Akt signaling pathway, cyclic adenosine 3,5-monophosphate (cAMP) signaling pathway, mitogen-activated protein kinase (MAPK) signaling pathway, and hypoxia-inducible factor-1 (HIF-1) signaling pathway were likely involved in the regulation of diabetic retinopathy. Compared with the control group, the expression of lncZNRD1-AS1 was significantly increased in retinal microvascular endothelial cells after treatment with high glucose for 24 h. Silencing lncZNRD1 promoted high glucose-induced apoptosis of microvascular endothelial cells. Additionally, silencing lncZNRD1 increased the expression levels of ALDH7A1 and ALDH3A2. In conclusion, lncZNRD1-AS1 demonstrated potentially beneficial function against high glucose-induced retina cell injury by regulating ALDH7A1 and ALDH3A2 expressions.
本研究旨在筛选与糖尿病视网膜病变发病机制相关的差异表达长链非编码 RNA（lncRNA），并验证 lncZNRD1 在高糖诱导的视网膜微血管内皮细胞损伤中的作用。收集正常和糖尿病大鼠的视网膜组织进行差异表达 lncRNA 的高通量测序。用 50mM 葡萄糖处理视网膜微血管内皮细胞 4、8、24、48 和 72 小时。结果表明，与对照组相比，模型组视网膜组织中有 736 个差异表达的 lncRNA，包括 226 个上调基因和 736 个下调基因。基于差异表达的 lncRNAs，京都基因与基因组百科全书（KEGG）分析表明，表皮生长因子受体（ErbB）信号通路、转化生长因子-（TGF-）信号通路、PI3K-Akt 信号通路、环磷酸腺苷（cAMP）信号通路、丝裂原激活蛋白激酶（MAPK）信号通路和缺氧诱导因子-1（HIF-1）信号通路可能参与了糖尿病视网膜病变的调控。与对照组相比，高糖处理 24 小时后，视网膜微血管内皮细胞中 lncZNRD1-AS1 的表达明显增加。沉默 lncZNRD1 促进了高糖诱导的微血管内皮细胞凋亡。此外，沉默 lncZNRD1 增加了 ALDH7A1 和 ALDH3A2 的表达水平。总之，lncZNRD1-AS1 通过调节 ALDH7A1 和 ALDH3A2 的表达，对高糖诱导的视网膜细胞损伤表现出潜在的有益作用。
