炎症
ICAM-1
细胞间粘附分子-1
内皮
生物
细胞粘附分子
免疫学
细胞生物学
内分泌学
作者
Yuhong Luo,Juan Feng,Qingbo Xu,Wengong Wang,Xian Wang
出处
期刊:Circulation Research
[Ovid Technologies (Wolters Kluwer)]
日期:2016-03-18
卷期号:118 (6): 944-956
被引量:66
标识
DOI:10.1161/circresaha.115.307674
摘要
Rationale : Vascular endothelial inflammation, including the expression of intercellular adhesion molecule 1 (ICAM-1), is a key event in vascular diseases. However, the mechanisms underlying the regulation of ICAM-1 are largely unknown. Objective : To investigate the mechanisms on the regulation of ICAM-1 by NOP2/Sun domain family, member 2 (NSun2)-mediated mRNA methylation and the impact of NSun2–ICAM-1 regulatory process in vascular inflammation and allograft arteriosclerosis. Methods and Results : By using in vitro, in cells, and in vivo methylation assays, we showed that the tRNA methyltransferase NSun2 methylated the ICAM-1 mRNA. Methylation by NSun2 promoted the translation of ICAM-1, thereby increasing the adhesion of leukocytes to endothelial cells. Tumor necrosis factor-α or homocysteine activated the methyltransferase activity of NSun2 by repressing the phosphorylation of NSun2 by Aurora-B. The levels of ICAM-1 induction and of leukocyte adhesion to vascular endothelium observed with homocysteine treatment in wild-type rats were markedly decreased in NSun2 −/− rats. In a rat model of aortic allograft, the lack of donor NSun2 impaired the formation of allograft arteriosclerosis. Conclusions : NSun2 upregulates the expression of ICAM-1 by methylating ICAM-1 mRNA. This regulatory process impacts on vascular inflammation and allograft arteriosclerosis.
科研通智能强力驱动
Strongly Powered by AbleSci AI