MicroRNAs in Hyperglycemia Induced Endothelial Cell Dysfunction

被引:68
|
作者
Silambarasan, Maskomani [1 ]
Tan, Jun Rong [1 ]
Karolina, Dwi Setyowati [1 ]
Armugam, Arunmozhiarasi [1 ]
Kaur, Charanjit [2 ]
Jeyaseelan, Kandiah [1 ,3 ]
机构
[1] Natl Univ Singapore, Dept Biochem, NUS Med, Singapore 117596, Singapore
[2] Natl Univ Singapore, Dept Anat, NUS Med, Singapore 117594, Singapore
[3] Monash Univ, Sch Biomed Sci, Dept Anat & Dev Biol, Fac Med Nursing & Hlth Sci, Clayton, Vic 3800, Australia
基金
英国医学研究理事会;
关键词
microRNA; diabetes mellitus; endothelial dysfunction; apoptosis; hyperglycemia; SPHINGOSINE-1-PHOSPHATE RECEPTOR 1; DIABETES-MELLITUS; INDUCED APOPTOSIS; UP-REGULATION; MOLECULAR-MECHANISMS; PROMOTES APOPTOSIS; OXIDATIVE STRESS; LIVER METASTASIS; CANCER CELLS; EXPRESSION;
D O I
10.3390/ijms17040518
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Hyperglycemia is closely associated with prediabetes and Type 2 Diabetes Mellitus. Hyperglycemia increases the risk of vascular complications such as diabetic retinopathy, diabetic nephropathy, peripheral vascular disease and cerebro/cardiovascular diseases. Under hyperglycemic conditions, the endothelial cells become dysfunctional. In this study, we investigated the miRNA expression changes in human umbilical vein endothelial cells exposed to different glucose concentrations (5, 10, 25 and 40mMglucose) and at various time intervals (6, 12, 24 and 48 h). miRNA microarray analyses showed that there is a correlation between hyperglycemia induced endothelial dysfunction and miRNA expression. In silico pathways analyses on the altered miRNA expression showed that the majority of the affected biological pathways appeared to be associated to endothelial cell dysfunction and apoptosis. We found the expression of ten miRNAs (miR-26a-5p, -26b-5p, 29b-3p, -29c-3p, -125b-1-3p, -130b-3p, -140-5p, -192-5p, -221-3p and -320a) to increase gradually with increasing concentration of glucose. These miRNAs were also found to be involved in endothelial dysfunction. At least seven of them, miR-29b-3p, -29c-3p, -125b-1-3p, -130b-3p, -221-3p, -320a and -192-5p, can be correlated to endothelial cell apoptosis.
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页数:22
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