Identification of lncRNAs Associated with the Pathogenesis of Diabetic Retinopathy: From Sequencing Analysis to Validation via In Vivo and In Vitro Experiments

Abstract

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-) β 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.

Aldehyde Dehydrogenase and Aldo-Keto Reductase Enzymes: Basic Concepts and Emerging Roles in Diabetic Retinopathy

“…The retinal abnormalities in SLS are likely attributable to the accumulation of lipid aldehydes and/or alcohols; however, further research is needed to identify the specific mechanisms involved. In the diabetic retina, ALDH3a2 is downregulated at the mRNA level [117], while both gene and protein levels are decreased in retinal endothelial cells exposed to high glucose conditions [143]. These changes are potentially linked to the upregulation of a specific long non-coding RNA known as lncZNRD1, which is induced by hyperglycemia [143].…”

“…In the diabetic retina, ALDH3a2 is downregulated at the mRNA level [117], while both gene and protein levels are decreased in retinal endothelial cells exposed to high glucose conditions [143]. These changes are potentially linked to the upregulation of a specific long non-coding RNA known as lncZNRD1, which is induced by hyperglycemia [143]. Notably, when lncZNRD1 is silenced, a significant increase in the expression levels of ALDH3a2 is observed in retinal endothelial cells cultured under hyperglycemic conditions [143].…”

“…These changes are potentially linked to the upregulation of a specific long non-coding RNA known as lncZNRD1, which is induced by hyperglycemia [143]. Notably, when lncZNRD1 is silenced, a significant increase in the expression levels of ALDH3a2 is observed in retinal endothelial cells cultured under hyperglycemic conditions [143].…”

Retracted: Identification of lncRNAs Associated with the Pathogenesis of Diabetic Retinopathy: From Sequencing Analysis to Validation via In Vivo and In Vitro Experiments

“…This article has been retracted by Hindawi, as publisher, following an investigation undertaken by the publisher [1]. This investigation has uncovered evidence of systematic manipulation of the publication and peer-review process.…”