title: High glucose concentration induces endothelial cell proliferation by regulating cyclin-D2-related miR-98.
abstract: Cyclin D2 is involved in the pathology of vascular complications of type 2 diabetes mellitus (T2DM). This study investigated the role of cyclin-D2-regulated miRNAs in endothelial cell proliferation of T2DM. Results showed that higher glucose concentration (4.5 g/l) significantly promoted the proliferation of rat aortic endothelial cells (RAOECs), and significantly increased the expression of cyclin D2 and phosphorylation of retinoblastoma 1 (p-RB1) in RAOECs compared with those under low glucose concentration. The cyclin D2-3' untranslated region is targeted by miR-98, as demonstrated by miRNA analysis software. Western blot also confirmed that cyclin D2 and p-RB1 expression was regulated by miR-98. The results indicated that miR-98 treatment can induce RAOEC apoptosis. The suppression of RAOEC growth by miR-98 might be related to regulation of Bcl-2, Bax and Caspase 9 expression. Furthermore, the expression levels of miR-98 decreased in 4.5 g/l glucose-treated cells compared with those treated by low glucose concentration. Similarly, the expression of miR-98 significantly decreased in aortas of established streptozotocin (STZ)-induced diabetic rat model compared with that in control rats; but cyclin D2 and p-RB1 levels remarkably increased in aortas of STZ-induced diabetic rats compared with those in healthy control rats. In conclusion, this study demonstrated that high glucose concentration induces cyclin D2 up-regulation and miR-98 down-regulation in the RAOECs. By regulating cyclin D2, miR-98 can inhibit human endothelial cell growth, thereby providing novel therapeutic targets for vascular complication of T2DM.
authors: Department of Biochemistry and Molecular Biology, Binzhou Medical University, Yantai, Shandong, China.
authors: Xin-Xin
authors: XX
authors: Li
authors: Department of Biochemistry and Molecular Biology, Binzhou Medical University, Yantai, Shandong, China.
authors: Yue-Mei
authors: YM
authors: Liu
authors: Department of Biochemistry and Molecular Biology, Binzhou Medical University, Yantai, Shandong, China.
authors: You-Jie
authors: YJ
authors: Li
authors: Yantaishan Hospital, Yantai, Shandong, China.
authors: Ning
authors: N
authors: Xie
authors: Department of Biochemistry and Molecular Biology, Binzhou Medical University, Yantai, Shandong, China.
authors: Yun-Fei
authors: YF
authors: Yan
authors: Shandong China Traditional Medical Affiliated Hospital, Jinan, China.
authors: Yong-Liang
authors: YL
authors: Chi
authors: Department of Biochemistry and Molecular Biology, Binzhou Medical University, Yantai, Shandong, China.
authors: Ling
authors: L
authors: Zhou
authors: Department of Biochemistry and Molecular Biology, Binzhou Medical University, Yantai, Shandong, China.
authors: Shu-Yang
authors: SY
authors: Xie
authors: Department of Biochemistry and Molecular Biology, Binzhou Medical University, Yantai, Shandong, China.|Institute of Epidemiology, Binzhou Medical University, Yantai, Shandong, China.
authors: Ping-Yu
authors: PY
authors: Wang
mesh_terms: D020413:3' Untranslated Regions / Q000235:genetics; D000818:Animals; D001011:Aorta / Q000166:cytology; D017209:Apoptosis / Q000187:drug effects / Q000235:genetics; D001483:Base Sequence; D049109:Cell Proliferation / Q000187:drug effects; D056742:Cyclin D2 / Q000235:genetics / Q000378:metabolism*; D003921:Diabetes Mellitus, Experimental / Q000235:genetics / Q000473:pathology; D004195:Disease Models, Animal; D042783:Endothelial Cells / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology*; D005786:Gene Expression Regulation / Q000187:drug effects; D005947:Glucose / Q000633:toxicity*; D008297:Male; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D010766:Phosphorylation / Q000187:drug effects; D017207:Rats, Sprague-Dawley; D016160:Retinoblastoma Protein / Q000235:genetics / Q000378:metabolism
chemical_list: D020413:3' Untranslated Regions; D056742:Cyclin D2; C571630:MIRN98 microRNA-98, rat; D035683:MicroRNAs; D016160:Retinoblastoma Protein; D005947:Glucose
keywords: cell proliferation; cyclin D2; gene expression; miR-98; type 2 diabetes