Room of Physical Diagnostics, Clinical College of Medicine, Bengbu Medical College, Bengbu, Anhui, 233030, P.R. China.
Department of Endocrinology, First Affiliated Hospital of Bengbu Medical College, 287 Changhuai Road, Longzihu Zone, Bengbu, Anhui Province, 233004, People's Republic of China.
BMC Endocr Disord. 2020 Jul 20;20(1):107. doi: 10.1186/s12902-020-00593-6.
Diabetes mellitus is often associated with microvascular and macrovascular lesions, and hyperglycemia-induced vascular endothelial cell damage is a key factor.
We 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.
Among 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.
These observations may provide novel insights into the regulatory molecules and pathways of hyperglycemia-related endothelial dysfunction in diabetes-associated vascular disease.
糖尿病常伴有微血管和大血管病变,高血糖诱导的血管内皮细胞损伤是一个关键因素。
我们以人脐静脉内皮细胞(HUVEC)为模型,研究了高糖诱导损伤后受影响的长链非编码 RNA(lncRNA)和信使 RNA(mRNA)。将 HUVEC 在高(25mmol/L)或正常(5mmol/L)葡萄糖条件下培养 6 天,然后通过 RNA-seq 对 lncRNA 和蛋白编码转录物进行分析。
在筛选出的 40379 个 lncRNA 中,有 214 个上调(log2[fold-change]>1,FDR<0.05),197 个下调(log2[fold-change]<-1,FDR<0.05),对高糖有反应。此外,在筛选出的 28431 个蛋白编码基因中,有 778 个上调,998 个下调。共鉴定出 945 个 lncRNA/mRNA 对,包括 126 个差异表达的 lncRNA 预测靶向 201 个 mRNA,其中 26 个为顺式调控相互作用。相应的 lncRNA-mRNA 网络由 354 个 lncRNA 节点、1167 个 mRNA 节点和 9735 个边缘组成。数十个具有高程度的 lncRNA 可能在高糖诱导的 HUVEC 损伤中发挥重要作用,包括 ENST00000600527、NONHSAT037576.2、NONHSAT135706.2、ENST00000602127、NONHSAT200243.1、NONHSAT217282.1、NONHSAT176260.1、NONHSAT199075.1、NONHSAT067063.2、NONHSAT058417.2。
这些观察结果可能为糖尿病相关血管疾病中与高血糖相关的内皮功能障碍的调节分子和途径提供新的见解。