Endothelial-Enriched lncRNA Gm39822 Modulates Inflammation and Dysfunction in Non-Diabetic Endothelial Cells
Year: 2025
Type: article
Abstract: 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 when exposed to high glucose or inflammatory cytokines (TNF-α and IL-1β). 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-α, IL-1β, 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.
DOI: 10.3390/ijms26178147
Authors: Amit Chandra, Emre Bektik, Vinay Randhawa, Mark W. Feinberg
Institutions: Brigham and Women's Hospital, Harvard University
Language: English
Subfield: Physiology
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $3,499
Awards: Non-coding RNAs in ischemic myocardial disease and diabetes: discovery, pathobiology, and therapeutic intervention, miR-130b, angiogenesis, and diabetic critical limb ischemia, miR-615, AKT/eNOS signaling, and angiogenesis, G1340753469, LncRNA MERRICAL, macrophage chemotaxis, and diabetes-associated atherosclerosis, G1868627300, G1987768016, LncRNA MAARS, macrophage apoptosis, and atherosclerosis, G3960842837, G4394777654, KLF10, CD4+ T cells, and transplant arteriopathy, G4835617167, G5857948765, miR-181b, endothelial cells, and vascular inflammation, G6473108759, LncRNA SNHG12, vascular senescence, and atherosclerosis, G7100179172, G7768941498, G8102513419, G8143269829, G8727138790, G8769546965, G9000045135, G9000209921, G9000265587, G9000299743, Integrated Epithelial and Muscosal Biology
OpenAlex ID: W4413412096