Silambarasan Maskomani, Tan Jun Rong, Karolina Dwi Setyowati, Armugam Arunmozhiarasi, Kaur Charanjit, Jeyaseelan Kandiah
Department of Biochemistry, NUS Medicine, National University of Singapore, Singapore 117596, Singapore.
Department of Anatomy, NUS Medicine, National University of Singapore, Singapore 117594, Singapore.
Int J Mol Sci. 2016 Apr 7;17(4):518. doi: 10.3390/ijms17040518.
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 40 mM glucose) 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.
高血糖与糖尿病前期和2型糖尿病密切相关。高血糖会增加血管并发症的风险,如糖尿病视网膜病变、糖尿病肾病、外周血管疾病以及脑血管/心血管疾病。在高血糖条件下,内皮细胞会出现功能障碍。在本研究中,我们调查了人脐静脉内皮细胞在暴露于不同葡萄糖浓度(5、10、25和40 mM葡萄糖)以及不同时间间隔(6、12、24和48小时)时的miRNA表达变化。miRNA微阵列分析表明,高血糖诱导的内皮功能障碍与miRNA表达之间存在相关性。对改变的miRNA表达进行的计算机通路分析表明,大多数受影响的生物学通路似乎与内皮细胞功能障碍和凋亡有关。我们发现十种miRNA(miR-26a-5p、-26b-5p、29b-3p、-29c-3p、-125b-1-3p、-130b-3p、-140-5p、-192-5p、-221-3p和-320a)的表达随着葡萄糖浓度的增加而逐渐升高。这些miRNA也被发现参与内皮功能障碍。其中至少七种,即miR-29b-3p、-29c-3p、-125b-1-3p、-130b-3p、-221-3p、-320a和-192-5p,与内皮细胞凋亡相关。