Endothelial-enriched lncRNA Gm39822 modulates inflammation and dysfunction in non-diabetic endothelial cells

Endothelial dysfunction underlies several vascular complications including diabetes and atherosclerosis. However, the underlying role of long non-coding RNAs (lncRNAs) remains poorly understood. This study elucidated the role of lncRNA Gm39822 in regulating endothelial dysfunction under healthy and diabetic conditions. Our data revealed that Gm39822 is enriched and upregulated in non-diabetic endothelial cells (ECs) when exposed to high glucose or inflammatory cytokines (TNF-a and IL-1b). Gm39822 overexpression promoted the expression of vascular cell adhesion molecule-1 (VCAM-1) and the adhesion of leukocytes in non-diabetic ECs but not in diabetic ECs. Conversely, Gm39822 silencing reduced VCAM1 expression and leukocyte adhesion in non-diabetic ECs and not in diabetic ECs. Gm39822 deficiency reduced the expression of inflammatory mediators (including p-P65, P65, P50, p-P38, P38. P-ERK1/2 and ERK1/2) in non-diabetic ECs. Furthermore, Gm39822 knockdown inhibited the secretion of pro-inflammatory cytokines including TNF-a, IL-1b, and IL-6, suggesting that Gm39822 regulates EC inflammatory responses. Mechanistically, we identified C1D, a nuclear enriched corepressor, as an interacting partner of Gm39822 that could play an important role in mediating Gm39822 functions in non-diabetic ECs. Collectively, our results identify a novel lncRNA Gm39822 and provide insights into the molecular mechanisms underlying endothelial dysfunction. These findings highlight Gm39822 as a potential therapeutic target for mitigating vascular complications associated with non-diabetic endothelial dysfunction. Transcriptomic RNA-sequencing was performed in bEND.3 cells after ribodepletion and library construction by using standard library construction and Illumina HiSeq2500 V4 2x150 PE (Azenta). The RNA-Seq dataset comprised 4 samples each for GapmeR and Negative Control groups.