Abstract
BackgroundDiabetes mellitus is often associated with microvascular and macrovascular lesions, and hyperglycemia-induced vascular endothelial cell damage is a key factor.MethodsWe investigated long non-coding RNAs (lncRNAs) and mRNAs that are affected by hyperglycemia-induced damage using human umbilical vein endothelial cells (HUVECs) as a model. HUVECs were cultured under high (25 mmol/L) or normal (5 mmol/L) glucose conditions for 6 d, and then lncRNAs and protein-coding transcripts were profiled by RNA-seq.ResultAmong 40,379 lncRNAs screened, 214 were upregulated (log2 [fold-change] > 1, FDR < 0.05) and 197 were downregulated (log2 [fold-change] < − 1, FDR < 0.05) in response to high-glucose. Furthermore, among 28,431 protein-coding genes screened, 778 were upregulated and 998 were downregulated. A total of 945 lncRNA/mRNA pairs were identified, including 126 differentially expressed lncRNAs predicted to target 201 mRNAs, among which 26 were cis-regulatory interactions. The corresponding lncRNA-mRNA network was composed of 354 lncRNA nodes, 1167 mRNA nodes and 9735 edges. Dozens of lncRNAs with high degree may play important roles in high-glucose-induced HUVEC damage, including ENST00000600527, NONHSAT037576.2, NONHSAT135706.2, ENST00000602127, NONHSAT200243.1, NONHSAT217282.1, NONHSAT176260.1, NONHSAT199075.1, NONHSAT067063.2, NONHSAT058417.2.ConclusionThese observations may provide novel insights into the regulatory molecules and pathways of hyperglycemia-related endothelial dysfunction in diabetes-associated vascular disease.
Highlights
Diabetes mellitus is often associated with microvascular and macrovascular lesions, and hyperglycemia-induced vascular endothelial cell damage is a key factor
High glucose (HG) treatment of vascular endothelial cells is accompanied by increased expression of Long non-coding RNAs (lncRNAs) MIAT, and interference with MIAT can promote the proliferation, migration and abnormal angiogenesis of vascular endothelial cells induced by high glucose (HG) [24]
In order to further understand the role of lncRNA in endothelial cell injury in diabetes mellitus, we carried out high throughput sequencing using human umbilical vein endothelial cells (HUVECs) cultured under normal (CN) or HG conditions
Summary
Diabetes mellitus is often associated with microvascular and macrovascular lesions, and hyperglycemia-induced vascular endothelial cell damage is a key factor. LncRNAs play important regulatory roles in various diseases, such as cancers [12,13,14,15], atherosclerosis [15], neurodegeneration [11], autoimmune disorders [16,17,18,19,20], and chronic vascular disease [21] Data from both in vitro hyperglycemia induction and in vivo diabetes mellitus experiments have shown that lncRNA MALAT1 is highly expressed, and that inhibition of its expression can effectively improve endothelial cell inflammation and diabetic retinopathy [22, 23]. Knockout of lncRNA MEG3 can aggravate retinal vascular dysfunction and increase microvascular leakage and inflammation [26] These results suggest that lncRNAs may comprise novel therapeutic targets in hyperglycemia-related endothelial dysfunction or diabetes-induced vascular disease. In order to further understand the role of lncRNA in endothelial cell injury in diabetes mellitus, we carried out high throughput sequencing using human umbilical vein endothelial cells (HUVECs) cultured under normal (CN) or HG conditions
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